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15 pages, 5700 KiB

Open AccessArticle

Exposure to Benzo(a)pyrene Enhances Acetaminophen-Induced Liver Injury in Mice at Non-Hepatotoxic Doses

by Yina Montero-Pérez and Jesus Olivero-Verbel

Sci. Pharm. 2024, 92(2), 30; https://doi.org/10.3390/scipharm92020030 - 3 Jun 2024

Cited by 1 | Viewed by 1463

Abstract

Acetaminophen (APAP) is a widely used analgesic, especially for children. Its primary mechanism involves inhibiting cyclooxygenase enzymes and activating the endocannabinoid and TRPV1 systems. Though its toxicity is low, it can harm the liver in a dose-dependent manner. Low APAP doses can also [...] Read more.

Acetaminophen (APAP) is a widely used analgesic, especially for children. Its primary mechanism involves inhibiting cyclooxygenase enzymes and activating the endocannabinoid and TRPV1 systems. Though its toxicity is low, it can harm the liver in a dose-dependent manner. Low APAP doses can also increase pollutant-induced liver damage. Little is known about interactions between APAP and benzo[a]pyrene (B[a]P). This study aimed to assess if co-exposure to non-hepatotoxic doses of B[a]P and APAP causes liver injury in mice, exploring the underlying mechanisms. Female ICR mice received 50 mg/kg B[a]P or a vehicle for three days, followed by 200 mg/kg APAP or a vehicle. Liver injury was assessed through histopathological examination, serum transaminase activity, and gene expression analysis. In the B[a]P/APAP group, several histology changes were observed, including ballooning injury, steatosis, necrosis, inflammation, and apoptosis. Transaminase levels correlated with histopathological scores, and there was an increase in hepatic cytochrome P450 family 1 subfamily a member 1 (Cyp1a1) mRNA levels and a decrease in aryl hydrocarbon receptor (Ahr), cytochrome P450 family 2 subfamily e polypeptide 1 (Cyp2e1), superoxide dismutase 1 (Sod1), peroxisome proliferator activated receptor gamma (Ppar-γ), and caspase 3 (Casp3). This suggests that prior exposure to B[a]P makes mice more susceptible to APAP-induced liver injury, involving changes in gene expression related to metabolism, redox balance, and cell proliferation. Therefore, using therapeutic APAP doses after exposure to B[a]P could lead to liver injury. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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16 pages, 2478 KiB

Open AccessArticle

Effect of Edge Activator Combinations in Transethosomal Formulations for Skin Delivery of Thymoquinone via Langmuir Technique

by Hana Mohd, Katarzyna Dopierała, Anze Zidar, Amitkumar Virani and Bozena Michniak-Kohn

Sci. Pharm. 2024, 92(2), 29; https://doi.org/10.3390/scipharm92020029 - 27 May 2024

Cited by 1 | Viewed by 1541

Abstract

Thymoquinone (TQ), a bioactive compound found in Nigella sativa seeds, possesses diverse therapeutic properties for skin conditions. However, formulating TQ presents challenges due to its hydrophobic nature and chemical instability, which hinder its skin penetration. Transethosomes, as a formulation, offer an environment conducive [...] Read more.

Thymoquinone (TQ), a bioactive compound found in Nigella sativa seeds, possesses diverse therapeutic properties for skin conditions. However, formulating TQ presents challenges due to its hydrophobic nature and chemical instability, which hinder its skin penetration. Transethosomes, as a formulation, offer an environment conducive to enhancing TQ’s solubility, stability, and skin permeation. To optimize TQ transethosomal formulations, we introduced a combination of ionic and nonionic surfactants, namely Tween 20 and sodium lauryl sulfate (SLS) or sodium lauroyl glutamate (SLG). Surfactants play a crucial role in stabilizing the formulation, reducing aggregation, improving biocompatibility, and minimizing potential toxicity. We fine-tuned the formulation composition and gained insights into its interfacial behavior using the Langmuir monolayer technique. This method elucidated the interfacial properties and behavior of phospholipids in ethosome and transethosome formulations. Our findings suggest that monolayer studies can serve as the initial step in selecting surfactants for nanocarrier formulations based on their interfacial dilational rheology studies. It was found that the addition of surfactant to the formulation increased the elasticity considering the capability of transethosomes to significantly decrease their radius when permeating the skin barrier. The results of the dilational rheology experiments were most relevant to drug permeation through the skin for the largest amplitude of deformation. The combination of Tween 20 and SLS efficiently modified the rheological behavior of lipids, increasing their elasticity. This conclusion was supported by in vitro studies, where formulation F2 composed of Tween 20 and SLS demonstrated the highest permeation after 24 h (300.23 µg/cm²). Furthermore, the F2 formulation showed the highest encapsulation efficiency (EE) of 94%, surpassing those of the control and ethosomal formulations. Additionally, this transethosomal formulation exhibited antimicrobial activity against S. aureus, with a zone of inhibition of 26.4 ± 0.3 mm. Importantly, we assessed the cytotoxicity of both ethosomes and transethosomes at concentrations ranging from 3.5 µM to 50 µM on HaCaT cell lines and found no cytotoxic effects compared to TQ hydroethanolic solution. These results suggest the potential safety and efficacy of TQ transethosomal formulations. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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16 pages, 763 KiB

Open AccessArticle

Bioactive Components Analysis and Pharmacological Properties of Extracts and Metabolites of Lichen Umbilicaria crustulosa

by Jovica Tomović, Aleksandar Kočović, Marijana Anđić, Jovana Bradić, Nevena Zubić, Vladimir Jakovljević, Miroslav Sovrlić, Perica Vasiljević and Nedeljko Manojlović

Sci. Pharm. 2024, 92(2), 27; https://doi.org/10.3390/scipharm92020027 - 20 May 2024

Viewed by 1694

Abstract

Lichens, a diverse group of organisms, have a unique structure consisting of fungal filaments and photosynthetic partner cells. This research conducted a comprehensive chemical analysis and evaluation of the anti-inflammatory and antioxidant properties of methanolic and acetone extracts from Umbilicaria crustulosa lichen, along [...] Read more.

Lichens, a diverse group of organisms, have a unique structure consisting of fungal filaments and photosynthetic partner cells. This research conducted a comprehensive chemical analysis and evaluation of the anti-inflammatory and antioxidant properties of methanolic and acetone extracts from Umbilicaria crustulosa lichen, along with its isolated metabolites. The process involved separating atranorin and chloratranorin fractions, physodic acid, and gyrophoric acid. Secondary metabolites were identified using chromatographic and spectroscopic data. The total polyphenols content was determined spectrophotometrically. This study examined the antioxidant activity of extracts of the lichen U. crustulosa and the isolated fractions using three methods: DPPH scavenging activity, ABTS scavenging activity, and reducing power. This study also evaluated the acute oral toxicity and the anti-inflammatory activity of the extracts in Wistar albino rats. A higher content of the total phenolic compounds was found in the acetone extract, but antioxidant and anti-inflammatory activities were more prominent in the methanolic extract. The isolated atranorin and chloratranorin fractions and compound physodic acid showed the highest antioxidant activity. No toxic effects were noted in the acute oral toxicity study. This study highlights the potential of the investigated lichen as a valuable source of novel biological agents. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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22 pages, 6185 KiB

Open AccessArticle

Stability-Indicating UPLC-PDA-QDa Methodology for Carvedilol and Felodipine in Fixed-Dose Combinations Using AQbD Principles

by Jesús Alberto Afonso Urich, Viktoria Marko, Katharina Boehm, Raymar Andreina Lara Garcia, Anna Fedorko, Sharareh Salar-Behzadi and Dalibor Jeremic

Sci. Pharm. 2024, 92(2), 22; https://doi.org/10.3390/scipharm92020022 - 25 Apr 2024

Cited by 1 | Viewed by 2015

Abstract

The development of analytical procedures, in line with the recent regulatory requirements ICH Q2 (R2) and ICH Q14, is progressing, and it must be able to manage the entire life cycle of the methodology. This is also applicable to and especially challenging for [...] Read more.

The development of analytical procedures, in line with the recent regulatory requirements ICH Q2 (R2) and ICH Q14, is progressing, and it must be able to manage the entire life cycle of the methodology. This is also applicable to and especially challenging for combinations of drug substances and dosage form. A reliable and efficient, stability-indicating, MS-compatible, reverse-phase ultra-performance liquid chromatographic (UPLC^®) method was developed for the determination of carvedilol and felodipine in a combination oral dosage form. The development of the method, performed using analytical quality by design (AQbD) principles, was in line with the future regulatory requirements. Furthermore, the fixed-dose combination dosage forms are a clear solution to the polypharmacy phenomenon in the elderly population. The main factors evaluated were the mobile phase buffer, organic modifier, column, flow, and column temperature. The optimum conditions were achieved with a Waters Acquity HSS T3 (100 × 2.1 mm i.d., 1.8 µm) column at 38 °C, using ammonium acetate buffer (5 mM, pH 4.5) (Solution A) and MeOH (Solution B) as mobile phases in gradient elution (t = 0 min, 10% B; t = 1.5 min, 10% B; t = 12.0 min, 90% B; t = 13.0 min, 10% B; t = 15.5 min, 10% B) at a flow rate of 0.2 mL/min and UV Detection of 240 and 362 nm for carvedilol (CAV) and felodipine (FLP), respectively. The linearity was demonstrated over concentration ranges of 30–650 µg/mL (R² = 0.9984) (CAV) and 32–260 µg/mL (R² = 0.9996) (FLP). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability, and fixed-dose combination dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with improved knowledge, leading to high-quality data, lower operation costs, and minimum regulatory risk. Furthermore, this work paves the way for providing a platform of robust analytical methods for the simultaneous quantification of innovative on-demand new dose combinations. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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16 pages, 5997 KiB

Open AccessArticle

Design, Synthesis and Antimicrobial Potential of Conjugated Metallopeptides Targeting DNA

by Maria Camila Moreno-Ramirez, Adriana Stefania Arias-Bravo, Alberto Aragón-Muriel, César Alonso Godoy, Yamil Liscano, Jose Oñate Garzón and Dorian Polo-Cerón

Sci. Pharm. 2024, 92(2), 21; https://doi.org/10.3390/scipharm92020021 - 17 Apr 2024

Viewed by 2318

Abstract

Antimicrobial resistance threatens the effective prevention and treatment of an increasingly broad spectrum of infections caused by pathogenic microorganisms. This pressing challenge has intensified the search for alternative antibiotics with new pharmacological properties. Due to the chemical synergy between the biological activity of [...] Read more.

Antimicrobial resistance threatens the effective prevention and treatment of an increasingly broad spectrum of infections caused by pathogenic microorganisms. This pressing challenge has intensified the search for alternative antibiotics with new pharmacological properties. Due to the chemical synergy between the biological activity of antimicrobial peptides (AMPs) and the different modes of action, catalytic properties, and redox chemistry of metal complexes, metallopeptides have emerged in recent years as an alternative to conventional antibiotics. In the present investigation, peptide ligands conjugated with 5-carboxy-1,10-phenanthroline (Phen) were prepared by solid-phase peptide synthesis (SPPS), and the corresponding copper(II) metallopeptides, Cu-PhenKG and Cu-PhenRG (where K = lysine, R = arginine, and G = glycine), were synthesized and characterized. The antimicrobial activities of these compounds toward Gram-positive and Gram-negative bacteria, evaluated by the broth microdilution technique, indicate that the metal center in the metallopeptides increases the antimicrobial activity of the complexes against the conjugated peptide ligands. Minimum inhibitory concentration (MIC) values of 0.5 μg/mL for S. aureus with the Cu-PhenKG complex and 0.63 μg/mL for S. typhimurium with the Cu-PhenRG complex were obtained. The MIC values found for the conjugated peptides in all microorganisms tested were greater than 1.5 μg/mL. The interactions of the conjugated peptides and their metallopeptides with plasmid DNA were evaluated by agarose gel electrophoresis. Alterations on the replication machinery were also studied by polymerase chain reaction (PCR). The results indicate that the complexes interact efficiently with pBR322 DNA from E. coli, delaying the band shift. Furthermore, the resulting DNA–metallopeptide complex is not a useful template DNA because it inhibits PCR, since no PCR product was detected. Finally, molecular dynamics and molecular docking simulations were performed to better understand the interactions of the obtained compounds with DNA. The Cu-PhenRG complex shows a significantly higher number of polar interactions with DNA, suggesting a higher binding affinity with the biopolymer. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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23 pages, 2298 KiB

Open AccessArticle

Pharmacokinetic Simulation Study: Exploring the Impact of Clinical Parameters on Lamotrigine for Different Patient Populations with Implications for Liver Function Assessment and Therapeutic Drug Monitoring

by Bárbara Costa, Isabel Silva, José Carlos Oliveira, Henrique Reguengo and Nuno Vale

Sci. Pharm. 2024, 92(1), 15; https://doi.org/10.3390/scipharm92010015 - 28 Feb 2024

Cited by 2 | Viewed by 4117

Abstract

Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity. Patients with Type 2 Diabetes (TD2) and Non-Alcoholic Fatty Liver [...] Read more.

Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity. Patients with Type 2 Diabetes (TD2) and Non-Alcoholic Fatty Liver Disease (NAFLD) are identified as more susceptible to these adverse reactions. This exploratory analysis aims to identify clinical parameters influencing lamotrigine pharmacokinetics across diverse populations, shedding light on toxicity and therapeutic drug monitoring (TDM) considerations. Starting with a retrospective analysis of 41 lamotrigine-treated patients at Hospital Santo António reveals changes or deviations from normal levels in various blood parameters and significant correlations between these parameters. Serum level changes, including creatinine, albumin, gamma-glutamyl transferase, total bilirubin, and Vitamin B12, are observed, with strong negative correlations between Vitamin B12 and creatinine. Then, we used GastroPlus and DILIsym to explore the impact of clinical parameters on lamotrigine for different patient populations. We constructed a Physiologically Based Pharmacokinetic (PBPK) model for lamotrigine in GastroPlus, based on ADMET predictions and data from the literature, to simulate the pharmacokinetic variability of lamotrigine in different populations, and we visualized the impact of increasing lamotrigine dose on its plasma concentration–time profiles (200 mg, 400 mg, 600 mg, 1200 mg) and reduced bioavailability. At higher doses, it is possible that the saturation of metabolic pathways leads to the formation of toxic metabolites or intermediates. These metabolites may exert inhibitory effects on drug-metabolizing enzymes or disrupt normal physiological processes, thereby impeding the drug’s clearance and potentially lowering its bioavailability. In DILIsym, we investigated lamotrigine’s DILI potential for individuals with diabetes and NAFLD. The results demonstrated an increased risk, emphasizing the need for careful monitoring. This study underscores the importance of understanding lamotrigine’s pharmacokinetics for tailored treatment decisions, improved outcomes, and minimized adverse reactions. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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16 pages, 4225 KiB

Open AccessArticle

New Carriers for Bioadhesive Gastroretentive Drug Delivery Systems Based on Eudragit^® EPO/Eudragit^® L100 Interpolyelectrolyte Complexes

by Daria S. Gordeeva, Aleksandra V. Sitenkova (Bukhovets) and Rouslan I. Moustafine

Sci. Pharm. 2024, 92(1), 14; https://doi.org/10.3390/scipharm92010014 - 22 Feb 2024

Cited by 1 | Viewed by 3435

Abstract

The aim of this study was the analysis of interpolyelectrolyte complexes (IPECs) based on Eudragit^® EPO and Eudragit^® L100 as prospective carriers for gastroretentive drug delivery systems (GRDDS) using two model drugs: metronidazole (MZ) and acyclovir (ACR). Eudragit^® EPO/L100 IPECs [...] Read more.

The aim of this study was the analysis of interpolyelectrolyte complexes (IPECs) based on Eudragit^® EPO and Eudragit^® L100 as prospective carriers for gastroretentive drug delivery systems (GRDDS) using two model drugs: metronidazole (MZ) and acyclovir (ACR). Eudragit^® EPO/L100 IPECs with different pH concentrations were characterized by different degrees of swelling in mimicking fasted stomach medium (0.1 M HCl) and saved their shape for 6 h. The microenvironmental changes in IPEC structures in acidic medium were investigated using FT-IR spectroscopy, thermal and elemental analysis. IPEC samples showed bioadhesive properties that were not significantly different from the positive control (Carbopol) in the test with the mucin compacts. The release rate of metronidazole (class I BCS) from IPEC matrices increased with the increasing degree of swelling. IPEC 1 provided 49.62 ± 6.20% and IPEC 2 reached 87.69 ± 5.15% of metronidazole release after 6 h in mimicking fasted stomach medium (0.1 M HCl). The total amount of released acyclovir (class III BCS) from IPEC 1 was 25.76 ± 5.67% and from IPEC 2 was 21.48 ± 5.00%. Release of both drugs was controlled by relaxation of polymeric chains in matrices according to the Peppas–Sahlin model. According to the received results, investigated interpolymer complexes are prospects for further evaluation as carriers for gastroretentive bioadhesive systems. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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11 pages, 2743 KiB

Open AccessArticle

Attenuation of Pulmonary Damage Associated with COPD in a Cadmium-Exposed Model Due to the Administration of a siRNA Targeting PAD4

by Sergio Adrian Ocampo-Ortega, Sandra Edith Cabrera-Becerra, Vivany Maydel Sierra-Sanchez, Vanessa Giselle García-Rubio, Citlali Margarita Blancas-Napoles, Rodrigo Romero-Nava, Fengyang Huang, Enrique Hong, Asdrúbal Aguilera-Méndez and Santiago Villafaña

Sci. Pharm. 2024, 92(1), 12; https://doi.org/10.3390/scipharm92010012 - 4 Feb 2024

Viewed by 2389

Abstract

Chronic obstructive pulmonary disease (COPD), characterised by persistent airflow limitation during breathing, is considered to be the third leading cause of death worldwide. Among the mechanisms involved in this pathology is the excessive generation of neutrophil extracellular traps (NETs), which can induce an [...] Read more.

Chronic obstructive pulmonary disease (COPD), characterised by persistent airflow limitation during breathing, is considered to be the third leading cause of death worldwide. Among the mechanisms involved in this pathology is the excessive generation of neutrophil extracellular traps (NETs), which can induce an unwanted inflammatory response. These traps have been reported to be generated by the enzyme peptidyl arginine deiminase 4 (PAD4). The aim of this work is therefore to evaluate the effect of the administration of a siRNA targeting PAD4 on lung damage in a COPD animal model. Wistar rats weighing 300–350 g were administered cadmium chloride (5 mg/kg i.p.) every 24 h. Then, following one week of the administration of cadmium chloride, the PAD4-targeted siRNA was administered, and at the second week, lung function was measured, as were lung and heart weights, as well as PAD4 expression by RT-PCR. Our results showed that cadmium administration generated a COPD model, which increased PAD4 expression and decreased lung and heart weights and respiratory function. SiRNA administration partially reversed the changes associated with the COPD model. In conclusion, our results suggest that administration of an siRNA targeting PAD4 could improve respiratory function by decreasing lung and heart damage. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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8 pages, 903 KiB

Open AccessArticle

The Potential of Incorporating a Pharmacist-Only Medicine Category in Poland

by Tomasz Zaprutko, Józefina Sprawka, Barbara Maciuszek-Bartkowska, Piotr Ratajczak, Dorota Kopciuch, Anna Paczkowska and Krzysztof Kus

Sci. Pharm. 2024, 92(1), 11; https://doi.org/10.3390/scipharm92010011 - 4 Feb 2024

Viewed by 2199

Abstract

Pharmacists play an important role, being increasingly focused on patient care and pharmaceutical services. This trend is also noticeable in Poland. Thus, we aimed to study the opinions of Polish pharmacists to determine the potential for introducing a new category of pharmacist-only medicines [...] Read more.

Pharmacists play an important role, being increasingly focused on patient care and pharmaceutical services. This trend is also noticeable in Poland. Thus, we aimed to study the opinions of Polish pharmacists to determine the potential for introducing a new category of pharmacist-only medicines (POMs). This study was conducted during the COVID-19 pandemic. Hence, the survey (anonymous questionnaire consisting of 10 questions addressed to pharmacists) was only available in electronic form. A total of 500 correctly completed surveys were collected and subjected to further analysis. The vast majority of pharmacists (91.8%) revealed a willingness to expand their professional rights and 88% stated that the POMs implementation would be important. As a substance that should function as a POM instead of an OTC medicine, respondents most often indicated ketoprofen, sildenafil, and mometasone, accounting for 26.2%, 24.8%, and 24.4% of responses, respectively. In terms of funding pharmaceutical services, 54.2% of respondents indicated that costs should be covered partially by the patient and the payer. There is a clear need for the incorporation of the POM category in Poland. Polish pharmacists are anticipating the development of pharmaceutical services which should be partly covered by patients and payers. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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11 pages, 811 KiB

Open AccessCommunication

Compounded Hair Solutions and Foams Containing Minoxidil: Does the Color Change Impact Stability?

by Hudson C. Polonini and Carolina C. V. Silva

Sci. Pharm. 2023, 91(3), 39; https://doi.org/10.3390/scipharm91030039 - 15 Aug 2023

Viewed by 11249

Abstract

An increasing number of pharmacies around the world are producing hair solutions and foams containing minoxidil for alopecia, commonly using ready-to-use vehicles such as TrichoSol^TM or TrichoFoam^TM. However, it is paramount to determine the chemical and microbiological compatibility of these [...] Read more.

An increasing number of pharmacies around the world are producing hair solutions and foams containing minoxidil for alopecia, commonly using ready-to-use vehicles such as TrichoSol^TM or TrichoFoam^TM. However, it is paramount to determine the chemical and microbiological compatibility of these formulations so they can be safely implemented as vehicles of choice. Also, these products usually suffer from a change of color over time, which leads to many patients prematurely discontinuing treatment. As long-term treatment is recommended, this study aimed to assess the physical–chemical and microbiological stability and investigate the color change of compounded minoxidil formulations. For that, HPLC analyses and antimicrobial effectiveness testing were conducted in a bracketed study covering concentrations from 1.0% to 7.0% of minoxidil. HPLC, pH, and metals in 5.0% minoxidil compounded products were determined using ICP-MS to evaluate the mechanisms involved in their color change. The stability of the products varied from 120 to 380 days. The color change was remarkably noticeable, but apart from this parameter, no other quality attribute was affected throughout this period, including minoxidil content, which presented only minor fluctuations. No precipitation was observed, and pH was relatively stable. It is not expected that this yellow color will impact effectiveness. Finally, we created an indicative color chart of the behavior of minoxidil in the studied vehicles. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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16 pages, 2809 KiB

Open AccessArticle

Analytical Investigation of Forced Oxidized Anti-VEGF IgG Molecules: A Focus on the Alterations in Antigen and Receptor Binding Activities

by Ayhan Parlar, Busra Gurel, Mehmet Reşit Sönmez and Meral Yüce

Sci. Pharm. 2023, 91(3), 31; https://doi.org/10.3390/scipharm91030031 - 28 Jun 2023

Cited by 1 | Viewed by 4024

Abstract

Alterations in the biological activity of the molecules under stress conditions have not been documented as widely in the literature yet. This study was designed to reveal the functional impacts of various oxidation conditions on a model mAb, a commercial anti-VEGF IgG molecule. [...] Read more.

Alterations in the biological activity of the molecules under stress conditions have not been documented as widely in the literature yet. This study was designed to reveal the functional impacts of various oxidation conditions on a model mAb, a commercial anti-VEGF IgG molecule. The responses to antigen binding, cell proliferation, FcRn receptors, and C1q binding, which rarely appear in the current literature, were investigated. The authors report peptide mapping data, post-translational modification (PTM) analysis, cell proliferation performance, and antigen (VEGF), C1q, and FcRn binding activities of the mAb under various stress conditions. The oxidation-prone site of the mAb was determined as Met252 in the DTLMISR peptide. The VEGF binding activity and anti-cell proliferation activity of the mAbs did not alter, while C1q and FcRn binding capacity significantly decreased under oxidative stress conditions. The full report is vital for many scientific and industrial processes about mAbs. The authors recommend performing functional analyses in addition to the structural studies while investigating the impacts of stress factors on therapeutic mAbs. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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14 pages, 1635 KiB

Open AccessArticle

Escherichia coli (Lilly) and Saccharomyces cerevisiae (Novo) rDNA Glucagon: An Assessment of Their Actions When Supplied Selectively to Periportal Cells in the Bivascularly Perfused Rat Liver

by Lívia Bracht, Jorgete Constantin, Rosane Marina Peralta and Adelar Bracht

Sci. Pharm. 2023, 91(3), 29; https://doi.org/10.3390/scipharm91030029 - 24 Jun 2023

Viewed by 2167

Abstract

The actions of Eli Lilly-rDNA glucagon and Novo Nordisk-rDNA glucagon on glycogen catabolism and related parameters were investigated using the bivascularly perfused rat liver. The technique allows glucagon to be supplied to a selective portion of the hepatic periportal region (≈39%) when the [...] Read more.

The actions of Eli Lilly-rDNA glucagon and Novo Nordisk-rDNA glucagon on glycogen catabolism and related parameters were investigated using the bivascularly perfused rat liver. The technique allows glucagon to be supplied to a selective portion of the hepatic periportal region (≈39%) when the former is infused into the hepatic artery in retrograde perfusion. Both glucagon preparations were equally effective in influencing metabolism (glucose output, glycolysis and O₂ uptake) when supplied to all cells along the liver sinusoids. When only a selective periportal region of the liver was supplied with the hormone, however, the action of Novo Nordisk-rDNA glucagon was proportional to the accessible cell space, whereas the action of Eli Lilly-rDNA glucagon greatly exceeded the action that was expected for the accessible space. Chromatographically, both rDNA preparations were not pure, but their impurities were not the same. The impurities in Eli Lilly-rDNA glucagon resembled those found in the similarly acting pancreatic Eli Lilly glucagon. It was concluded that the space-extrapolating action of Eli Lilly-rDNA glucagon is caused by a yet-to-be-identified impurity. The hypothesis was raised that an impurity in certain glucagon preparations can enhance cell-to-cell propagation of the glucagon signal, possibly via gap junctional communication. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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20 pages, 7833 KiB

Open AccessArticle

Mapping Protein Targets of Carnosol, a Molecule Identified in Rosmarinus officinalis: In Silico Docking Studies and Network Pharmacology

by María Taboada-Alquerque, Danilo Pajaro-Valenzuela, Karina Caballero-Gallardo, Alejandro Cifuentes, Elena Ibáñez, Maicol Ahumedo-Monterrosa, Elena E. Stashenko and Jesus Olivero-Verbel

Sci. Pharm. 2023, 91(2), 19; https://doi.org/10.3390/scipharm91020019 - 10 Apr 2023

Viewed by 3846

Abstract

Carnosol is a natural diterpene present in Rosmarinus officinalis L. (rosemary) with anti-tumor and anti-inflammatory properties. Despite its importance, the pharmacological mechanisms underlying the interactions between carnosol and human targets are still unclear. The goal was to identify plausible human target for carnosol [...] Read more.

Carnosol is a natural diterpene present in Rosmarinus officinalis L. (rosemary) with anti-tumor and anti-inflammatory properties. Despite its importance, the pharmacological mechanisms underlying the interactions between carnosol and human targets are still unclear. The goal was to identify plausible human target for carnosol and the network pharmacology. Rosemary was analyzed using HPLC-QTOF-MS/MS. Potential carnosol targets were identified using docking and a public database (CTD). Carnosol was screened against 708 human proteins using AutoDock Vina, and affinity values were used as prioritization criteria. The targets set was uploaded to WebGestalt to obtain Gene Ontology (GO) and KEGG pathway enrichment analysis. HPLC-QTOF-MS/MS analyses allowed the tentative annotation of nine chemicals, with carnosol being the most ionized. There were 53 plausible targets for carnosol, with 20 identified using virtual screening, including Hsp90α (−10.9 kcal/mol), AKR1C3 (−10.4 kcal/mol), and Hsp90β (−10.4 kcal/mol), and 33 identified from CTD. The potential targets for carnosol identified with PPI and molecular docking were HSP90AA1, MAPK1, MAPK3, CAT, JUN, AHR, and CASP3. GO terms and KEGG pathways analysis found that carnosol is closely related to infection (Chagas, influenza A, toxoplasmosis, and pertussis) and inflammation (IL-17 and TNF signaling pathway and Th-17 cell differentiation). These results demonstrated that carnosol may induce an immuno-inflammatory response. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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14 pages, 2806 KiB

Open AccessArticle

Carthamus tinctorius Suppresses LPS-Induced Anti-Inflammatory Responses by Inhibiting the MAPKs/NF-κB Signaling Pathway in HaCaT Cells

by So-Yeon Kim, Minji Hong, Ponnuvel Deepa, Kandhasamy Sowndhararajan, Se Jin Park, SeonJu Park and Songmun Kim

Sci. Pharm. 2023, 91(1), 14; https://doi.org/10.3390/scipharm91010014 - 6 Mar 2023

Cited by 4 | Viewed by 3564

Abstract

This study aimed to elucidate the anti-inflammatory activity of C. tinctorius leaves by measuring inflammatory parameters such as nitric oxide (NO) production and mRNA expression of iNOS, interleukin-6 (IL-6), and IL-1β in lipopolysaccharide (LPS)-induced HaCaT cells. Further, the effect of C. tinctorius ethanol [...] Read more.

This study aimed to elucidate the anti-inflammatory activity of C. tinctorius leaves by measuring inflammatory parameters such as nitric oxide (NO) production and mRNA expression of iNOS, interleukin-6 (IL-6), and IL-1β in lipopolysaccharide (LPS)-induced HaCaT cells. Further, the effect of C. tinctorius ethanol extract on the MAPKs/NF-κB signaling pathway was examined in HaCaT cells. The phytochemical profile of the ethanol extract of C. tinctorius leaves was determined using UPLC-QTOF-MS/MS. The results indicated that the ethanol extract of C. tinctorius effectively attenuated LPS-induced secretion of NO, IL-6, and IL-1β in HaCaT cells. Further, LPS-stimulated mRNA and protein expressions of iNOS were decreased by pre-treatment with C. tinctorius ethanol extract at the transcriptional level in HaCaT cells. Moreover, the ethanol extract of C. tinctorius suppressed NF-κB signaling in LPS-induced HaCaT cells. This suppression was mediated by MAPKs/NF-κB signaling, inhibiting the phosphorylation of p38 and p65 in HaCaT cells. However, there is no significant effect on the phosphorylation of JNK by the ethanol extract. The QTOF-MS/MS analysis revealed the identification of 27 components in the ethanol extract of C. tinctorius leaves. The data demonstrate that the ethanol extract of C. tinctorius leaves protects the LPS-induced HaCaT cells by inhibiting the expression of iNOS, IL-6, and IL-1β and suppressing the phosphorylation of the p38, p65, p-JNK via inactivation of MAPKs/NF-κB signaling pathway. These results demonstrate that C. tinctorius leaves may serve as a potential candidate to prevent inflammation-related diseases. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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9 pages, 3234 KiB

Open AccessArticle

Detailing the Ten Main Professional Roles of a Pharmacist to Provide the Scope of Professional Functions

by Yuliia Kremin, Lilia Lesyk, Roman Lesyk, Oksana Levytska and Bohdan Hromovyk

Sci. Pharm. 2023, 91(1), 5; https://doi.org/10.3390/scipharm91010005 - 13 Jan 2023

Cited by 5 | Viewed by 13410

Abstract

As members of a public trust profession, pharmacists are the most accessible medical team members. Therefore, every pharmacist must know the scope of their professional roles (PR) and professional functions (PF). The study aimed to detail the major PR into a pooled set [...] Read more.

As members of a public trust profession, pharmacists are the most accessible medical team members. Therefore, every pharmacist must know the scope of their professional roles (PR) and professional functions (PF). The study aimed to detail the major PR into a pooled set of PF. The research materials were the provisions of the World Health Organization, the International Pharmaceutical Federation, and scientific works on the PR of pharmacists. Methods of critical analysis, concretization, functional decomposition, and scientific generalization were used. As a result of detailing the 10 main PR according to the “ten-star pharmacist” concept for each, a combined set of partial PFs of the pharmacist was obtained. The decomposition takes into account the principle of complexity limitation, which allowed three to six partial PF for the respective PR to be obtained, namely: three PFs for a life-long-learner, five PFs for a caregiver, a decision-maker, a teacher, a leader, a researcher, an entrepreneur, and an agent of positive change, six PFs for a communicator and a manager. Thus, due to the decomposition of each of the 10 main PR of the pharmacist into three or six corresponding partial PFs, we received a multifunctional verbal model of difficult to organize, professional activities, which is identified by a total of 50 PFs. The importance of using this model in formulating professional competencies and learning outcomes of educational programs for pharmacists is emphasized. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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11 pages, 758 KiB

Open AccessArticle

Effect of Aqueous Extracts of Quercus resinosa on the Mechanical Behavior of Bigels

by José Alberto Gallegos-Infante, María del Pilar Galindo-Galindo, Martha Rocío Moreno-Jiménez, Nuria Elizabeth Rocha-Guzmán and Rubén Francisco González-Laredo

Sci. Pharm. 2022, 90(4), 73; https://doi.org/10.3390/scipharm90040073 - 28 Nov 2022

Cited by 5 | Viewed by 2543

Abstract

Quercus resinosa leaves are rich in polyphenol compounds, however, they are unstable to several chemical and physical factors that limit their activity. Several methods have been developed to solve such problems, among which bigels can be mentioned and obtained using hydrogels and oleogels. [...] Read more.

Quercus resinosa leaves are rich in polyphenol compounds, however, they are unstable to several chemical and physical factors that limit their activity. Several methods have been developed to solve such problems, among which bigels can be mentioned and obtained using hydrogels and oleogels. The mechanical characterization of this type of materials is by using rheological methods. Although the use of these methods is well documented, the Carreau-Yasuda model has been little used to evaluate the effect of polyphenols on the mechanical behavior of bigels. Therefore, bigels were obtained from hydrogels (guar gum/xanthan gum, 0.5/0.5% w/v) and oleogels (sesame oil/sorbitan monostearate 10% w/w). Micrographs, linear viscoelasticity range, frequency sweep, and single shear tests were performed. The data were analyzed using ANOVA and Tukey test (p < 0.05); micrographs showed linear relationship between polyphenols concentration and droplet size. Liquid fraction of bigels showed a pseudoplastic behavior, while the parameters of Carreau-Yasuda model showed that the highest value of the complex viscosity at zero shear was at the lowest concentration of extract; the relaxation time presented the lowest value at higher concentrations of extracts. These results indicate that the presence of polyphenols modifyes the mechanical behavior of bigels. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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19 pages, 2816 KiB

Open AccessArticle

New Quinazolin-4(3H)-one Derivatives Incorporating Hydrazone and Pyrazole Scaffolds as Antimicrobial Agents Targeting DNA Gyraze Enzyme

by Eman M. Mohi El-Deen, Eman S. Nossier and Eman A. Karam

Sci. Pharm. 2022, 90(3), 52; https://doi.org/10.3390/scipharm90030052 - 26 Aug 2022

Cited by 21 | Viewed by 2831

Abstract

The present work includes the synthesis of a new series of quinazolin-4(3H)-one compounds (4a–f, 5a–d) as antimicrobial agents. The starting compound, 2-hydrazinylquinazolin-4(3H)-one (2), was synthesized and treated with different carbonyl [...] Read more.

The present work includes the synthesis of a new series of quinazolin-4(3H)-one compounds (4a–f, 5a–d) as antimicrobial agents. The starting compound, 2-hydrazinylquinazolin-4(3H)-one (2), was synthesized and treated with different carbonyl compounds to afford the hydrazone derivatives 4a–f. In addition, the hydrazone derivatives 4a–d were treated with a DMF/POCl₃ mixture to give the formyl-pyrazole derivatives 5a–d. All the target compounds were evaluated as antimicrobial agents against four bacterial and four fungal strains. The majority of the tested compounds showed potent antimicrobial activity compared with the reference antibiotics. The most potent antimicrobial activity was shown by 5a with MIC values in the range (1–16) μg/mL. In addition, the most potent compounds against E. coli were evaluated for their inhibitory activity against E. coli DNA gyrase, whereas the target compounds 4a, 5a, 5c, and 5d showed the most potent inhibition to the target enzyme with IC₅₀ values ranging from 3.19 to 4.17 µM. Furthermore, molecular docking studies were performed for the most active compounds against the target E. coli DNA gyrase to determine their binding affinity within the enzyme’s active site. Moreover, ADME evaluations of these compounds predicted their high oral bioavailability and good GI absorption. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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12 pages, 690 KiB

Open AccessArticle

Antidepressant Effect of Neuropeptide Y in Models of Acute and Chronic Stress

by Nika Andriushchenko, Kira Nebogina, Yana Zorkina, Olga Abramova, Eugene Zubkov, Aleksandra Ochneva, Valeria Ushakova, Konstantin Pavlov, Olga Gurina, Vladimir Chekhonin and Anna Morozova

Sci. Pharm. 2022, 90(3), 50; https://doi.org/10.3390/scipharm90030050 - 23 Aug 2022

Cited by 2 | Viewed by 2838

Abstract

The search for potential effective antidepressants with minimal side effects is necessary. Peptides are possible applicants for this role. We investigated the antidepressant effect of neuropeptide Y (NY), alone and in combination with clomipramine, in models of acute and chronic stress induced by [...] Read more.

The search for potential effective antidepressants with minimal side effects is necessary. Peptides are possible applicants for this role. We investigated the antidepressant effect of neuropeptide Y (NY), alone and in combination with clomipramine, in models of acute and chronic stress induced by ultrasound of variable frequencies. Rats were divided into the following groups: the control group, stress group, and stress groups with intranasal administration of NY (100 μg/kg) or clomipramine (7.5 mg/kg), or their combination. Rat behavior was evaluated using a sucrose preference test and forced swimming test in an acute stress model, and a sucrose preference test, forced swimming test, social interaction test, open field test, and Morris water maze test in a chronic stress model. The results of our experiment demonstrated a protective effect of intranasal NY in a model of acute stress, which was comparable to the antidepressant effect of clomipramine. When the same dose was chronically administered, NY also demonstrated an antidepressant action, although expressed in a lesser degree than clomipramine. The combination of NY and clomipramine was much less effective in the chronic stress paradigm compared to the separated drug administration, but was just as effective in the acute stress paradigm. Until now, there was no convincing evidence for the efficacy of the chronic administration of neuropeptide Y; we demonstrated its effectiveness in the animal model of depressive-like behavior. However, our hypothesis that neuropeptide Y can enhance the effect of a classical antidepressant was not confirmed. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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11 pages, 4344 KiB

Open AccessArticle

Synthesis and Evaluation of (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists

by Edward A. Wetzel, Grace C. Corriero, Sandra Brown-Ford, Daniel S. Sem and William A. Donaldson

Sci. Pharm. 2022, 90(3), 46; https://doi.org/10.3390/scipharm90030046 - 1 Aug 2022

Cited by 1 | Viewed by 3597

Abstract

Estrogen receptors (ER) are nuclear hormone receptors which are responsible for sex hormone signaling in women. A series of (1,4-disubstituted)-1,2,3-triazoles 5–21 were prepared by reaction of azidophenols with terminal alkynes under Fokin reaction conditions. The products were purified by column chromatography [...] Read more.

Estrogen receptors (ER) are nuclear hormone receptors which are responsible for sex hormone signaling in women. A series of (1,4-disubstituted)-1,2,3-triazoles 5–21 were prepared by reaction of azidophenols with terminal alkynes under Fokin reaction conditions. The products were purified by column chromatography or recrystallization and characterized by NMR and HRMS. The compounds were tested for binding to ERβ via a ligand displacement assay, and 1-(4-hydroxyphenyl)-α-phenyl-1,2,3-triazole-4-ethanol (21) was found to be the most potent analog (EC₅₀ = 1.59 μM). Molecular docking of 5–21 within the ligand binding pocket of ERβ (pdb 2jj3) was performed and the docking scores exhibited a general qualitative trend consistent with the measured EC₅₀ values. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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16 pages, 3506 KiB

Open AccessArticle

Emerging Approach for the Application of Hibiscus sabdariffa Extract Ointment in the Superficial Burn Care

by Rania Khalil, Galal Yahya, Walied S. Abdo, Ghada S. El-Tanbouly, Dina Johar, Mahmoud Saad Abdel-Halim, Hanan Eissa, Calin Magheru, Sameh Saber and Simona Cavalu

Sci. Pharm. 2022, 90(3), 41; https://doi.org/10.3390/scipharm90030041 - 30 Jun 2022

Cited by 6 | Viewed by 4006

Abstract

Wound healing comprises organized events involving tissue repair and regeneration. The discovery of toll-like receptors (TLRs) sheds recent light on the mechanisms involved in initiating inflammatory responses throughout the healing cascades. Hibiscus sabdariffa (HS) components may exhibit a wound healing action, owing to [...] Read more.

Wound healing comprises organized events involving tissue repair and regeneration. The discovery of toll-like receptors (TLRs) sheds recent light on the mechanisms involved in initiating inflammatory responses throughout the healing cascades. Hibiscus sabdariffa (HS) components may exhibit a wound healing action, owing to their antioxidant and anti-inflammatory activities. This study was designed to investigate the early effects of HS loaded in an ointment base on wound healing, antioxidant, antimicrobial effects, burning intensity, and histopathological features on the rat burn model in comparison to the standard treatment, Iruxol^® ointment. A burn injury model was used to evaluate the wound healing potency of the preparation. Rats were treated with ointments three times on the day of the induction of the burn. Findings revealed that the strong antioxidant properties of the HS-loaded ointment augmented the skin healing potential by stimulating biomarkers required for skin regeneration. HS repressed the burning-induced inflammation by the effective reduction in the levels of tumor necrosis factor α (TNF-α) and IL-6 through TLR4 protein inhibition. Topical HS downregulates transforming growth factor-beta (TGF-β) levels. HS extract possesses a potential bactericidal activity against highly resistant clinical isolates of Pseudomonas aeruginosa. Overall, this study proclaims that HS-loaded topical preparations could be a valuable product that serves as adjuvants to accelerate burn wound healing through inactivating the TLR4 pathway. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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18 pages, 2710 KiB

Open AccessArticle

Colorectal Cancer Chemoprevention by S-Allyl Cysteine–Caffeic Acid Hybrids: In Vitro Biological Activity and In Silico Studies

by Angie Herrera-Ramirez, Andres F. Yepes-Pérez, Jorge Quintero-Saumeth, Gustavo Moreno-Quintero, Tonny W. Naranjo and Wilson Cardona-Galeano

Sci. Pharm. 2022, 90(3), 40; https://doi.org/10.3390/scipharm90030040 - 30 Jun 2022

Cited by 6 | Viewed by 3807

Abstract

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed at late stages, when the tumor has disseminated to other organs. Moreover, it is common to observe that malignant cells may acquire resistance to [...] Read more.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed at late stages, when the tumor has disseminated to other organs. Moreover, it is common to observe that malignant cells may acquire resistance to conventional chemotherapies through different mechanisms, including reducing drug activation or accumulation (by enhancing efflux), inducing alterations in molecular targets, and inhibiting the DNA damage response, among other strategies. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) that exhibited selective cytotoxicity against SW480 cells, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated the possible mechanisms of these molecules in greater depth, to identify whether they could be valuable therapeutic scaffolds in the search for new molecules with chemopreventive potential for the treatment of CRC. Both compounds reduced ROS formation, which could be related to antioxidant effects. Further evaluations showed that SAC-CAFA-MET induces cell death independent of caspases and the tumor-suppressor protein p53, but probably mediated by the negative regulation of the pro-apoptotic Bcl-2. In addition, the lack of activation of caspase-8 and the positive regulation of caspase-3 induced by SAC-CAFA-PENT suggest that this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathways. Furthermore, the downregulation of IL-6 by SAC-CAFA-PENT suggests that it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which SAC-CAFA-PENT elicits apoptosis in SW480human colorectal adenocarcinoma cells. Meanwhile, density functional theory (DFT) calculations suggest that both hybrids would produce effects in the modulation of ROS in SW480 cells via the hydrogen atom transfer (HAT) pathway. The present work notes that SAC-CAFA-MET and SAC-CAFA-PENT could be potential candidates for further investigations in the search for potential chemopreventive agents. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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15 pages, 1601 KiB

Open AccessArticle

In Vitro and In Silico Antistaphylococcal Activity of Indole Alkaloids Isolated from Tabernaemontana cymosa Jacq (Apocynaceae)

by Yina Pájaro-González, Julián Cabrera-Barraza, Geraldine Martelo-Ramírez, Andrés F. Oliveros-Díaz, Juan Urrego-Álvarez, Wiston Quiñones-Fletcher and Fredyc Díaz-Castillo

Sci. Pharm. 2022, 90(2), 38; https://doi.org/10.3390/scipharm90020038 - 14 Jun 2022

Cited by 4 | Viewed by 3319

Abstract

The species of the genus Tabernaemontana have a long tradition of use in different pathologies of infectious origins; the antibacterial, antifungal, and antiviral effects related to the control of the pathologies where the species of this genus are used, have been attributed to [...] Read more.

The species of the genus Tabernaemontana have a long tradition of use in different pathologies of infectious origins; the antibacterial, antifungal, and antiviral effects related to the control of the pathologies where the species of this genus are used, have been attributed to the indole monoterpene alkaloids, mainly those of the iboga type. There are more than 1000 alkaloids isolated from different species of Tabernaemontana and other genera of the Apocynaceae family, several of which lack studies related to antibacterial activity. In the present study, four monoterpene indole alkaloids were isolated from the seeds of the species Tabernaemontana cymosa Jacq, namely voacangine (1), voacangine-7-hydroxyindolenine (2), 3-oxovoacangine (3), and rupicoline (4), which were tested in an in vitro antibacterial activity study against the bacteria S. aureus, sensitive and resistant to methicillin, and classified by the World Health Organization as critical for the investigation of new antibiotics. Of the four alkaloids tested, only voacangine was active against S. aureus, with an MIC of 50 µg/mL. In addition, an in silico study was carried out between the four isolated alkaloids and some proteins of this bacterium, finding that voacangine also showed binding to proteins involved in cell wall synthesis, mainly PBP2 and PBP2a. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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15 pages, 2647 KiB

Open AccessArticle

Ex Vivo and In Vivo Study of Some Isoquinoline Precursors

by Miglena Milusheva, Vera Gledacheva, Margarita Batmazyan, Stoyanka Nikolova, Iliyana Stefanova, Darinka Dimitrova, Kremena Saracheva, Desislav Tomov and Veneta Chaova-Gizdakova

Sci. Pharm. 2022, 90(2), 37; https://doi.org/10.3390/scipharm90020037 - 13 Jun 2022

Cited by 8 | Viewed by 2927

Abstract

This article concerns the synthesis and biological activities of some N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides as isoquinoline precursors and compounds with smooth muscle (SM) relaxant activity. Aim: find the biological activity of N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides and compare it with papaverine, an isoquinoline alkaloid that has been known [...] Read more.

This article concerns the synthesis and biological activities of some N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides as isoquinoline precursors and compounds with smooth muscle (SM) relaxant activity. Aim: find the biological activity of N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides and compare it with papaverine, an isoquinoline alkaloid that has been known as a brain and coronary vasodilator and SM relaxant. Materials and methods: In silico simulation with the PASS online program predicts SM relaxant activity for the compounds. The amides were tested on the isolated gastric SM preparations (SMPs) from rats to determine their effects on spontaneous contractile activity (CA) compared with papaverine. The in vivo effect on the learning and memory processes of rats was also assessed. Results: the data from the isometric measurements showed that one of the compounds caused ex vivo relaxation in circular SM tissues isolated from the stomach (corpus) of male Wistar rats. Conclusion: We found that the compound’s SM relaxation uses the papaverine pathway. It also has an improving effect on the cognitive functions of learning and memory processes in rats. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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12 pages, 1079 KiB

Open AccessArticle

Comparison of the Purity and Impurity of Glucagon-for-Injection Products under Various Stability Conditions

by Zhongli Bao, Ya-Chi Cheng, Mary Ziping Luo and Jack Yongfeng Zhang

Sci. Pharm. 2022, 90(2), 32; https://doi.org/10.3390/scipharm90020032 - 17 May 2022

Cited by 3 | Viewed by 4015

Abstract

Glucagon is a polypeptide hormone that serves as an essential therapeutic agent in the emergency treatment of hypoglycemia. Recently, the first generic glucagon for injection was approved. However, unlike its brand name counterpart, which is produced via recombinant DNA, the generic glucagon is [...] Read more.

Glucagon is a polypeptide hormone that serves as an essential therapeutic agent in the emergency treatment of hypoglycemia. Recently, the first generic glucagon for injection was approved. However, unlike its brand name counterpart, which is produced via recombinant DNA, the generic glucagon is produced using a chemical synthesis method. Regardless of its origin, impurities may occur in both glucagon drug products. While these impurities may greatly compromise the safety and efficacy of the glucagon drug products, studies accessing the impurities of glucagon for injection are limited. This manuscript analyzed the stability and impurities of a generic and brand glucagon for injection, including desamido and non-desamido impurities, under various storage and temperature conditions using an ultra-performance liquid chromatography method. The glucagon products were analyzed after 6 and 24 months of storage under room temperatures (20–25 °C). In addition, the products were also assessed after 6 months of storage under high temperatures (40 °C). Under each stability storage condition, three lots of the synthetic glucagon were evaluated by UPLC with at least one lot of the recombinant glucagon for comparison. A total of 37 peaks were identified (except for the solvent peaks, which appeared at retention times less than 1.5 min) from the synthetic and recombinant glucagon lots. It was found that the number of impurities observed in the synthetic glucagon were lower than the referenced recombinant glucagon across all stability conditions. Throughout all tested conditions, the synthetic glucagon for injection had an averaged purity of 92.8–99.3%, while the referenced recombinant drug had an averaged purity of 70.3–91.7%. Based on the study results, it can be concluded that the impurity profile for the synthetic glucagon for injection has a comparable and even lower level of impurities than the recombinant version under all stability conditions. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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9 pages, 829 KiB

Open AccessArticle

Gossypol from Gossypium spp. Inhibits Helicobacter pylori Clinical Strains and Urease Enzyme Activity: Bioactivity and Safety Assessments

by Miroslava Šudomová and Sherif T. S. Hassan

Sci. Pharm. 2022, 90(2), 29; https://doi.org/10.3390/scipharm90020029 - 5 May 2022

Cited by 4 | Viewed by 3338

Abstract

This study investigates the inhibitory activities of gossypol, a natural polyphenolic compound from Gossypium spp., against Helicobacter pylori (HP) clinical strains and a urease enzyme that plays a key role in the pathogenesis of HP. Gossypol was detected to exhibit a bacteriostatic action [...] Read more.

This study investigates the inhibitory activities of gossypol, a natural polyphenolic compound from Gossypium spp., against Helicobacter pylori (HP) clinical strains and a urease enzyme that plays a key role in the pathogenesis of HP. Gossypol was detected to exhibit a bacteriostatic action against all the HP strains tested with minimum inhibitory concentration (MIC) values ranging from 3.51 to 4.14 µg/mL. The activity of HP urease (HPU) was efficiently impeded by gossypol with a 50% inhibitory concentration (IC₅₀) value of 3.3 µM using an Electrospray Ionization–Mass Spectrometry (ESI-MS)-based method. The in vitro cytotoxicity assay showed no significant cytotoxic properties of gossypol against human gastric epithelial cells. Additionally, molecular docking studies were performed to assess the binding mode and the molecular interactions of gossypol with HPU with a binding affinity value of −8.1 kcal/mol compared with an HPU–acetohydroxamic acid (a standard urease inhibitor) docking complex (–6.1 kcal/mol). The overall results reveal that gossypol might help fight against HP infection by two mechanisms of action: inhibition of the growth of HP and inhibition of urease. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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8 pages, 1284 KiB

Open AccessArticle

Preclinical Safety Profile of an Oral Naringenin/Hesperidin Dosage Form by In Vivo Toxicological Tests

by Carla Georgina Cicero-Sarmiento, Rolffy Ortiz-Andrade, Jesús Alfredo Araujo-León, Maira Rubí Segura-Campos, Priscila Vazquez-Garcia, Héctor Rubio-Zapata, Efrén Hernández-Baltazar, Victor Yañez-Pérez, Amanda Sánchez-Recillas, Juan Carlos Sánchez-Salgado, Emanuel Hernández-Núñez and Durcy Ruiz-Ciau

Sci. Pharm. 2022, 90(2), 28; https://doi.org/10.3390/scipharm90020028 - 2 May 2022

Cited by 4 | Viewed by 3967

Abstract

We developed a naringenin–hesperidin molar mixture (MIX–160) with proven antihyperglycemic and vasorelaxant activity in preclinical studies. A solid dosage form was manufactured to improve the bioavailability properties. In the current study, we sought to evaluate the oral preclinical toxicity of the MIX–160 dosage [...] Read more.

We developed a naringenin–hesperidin molar mixture (MIX–160) with proven antihyperglycemic and vasorelaxant activity in preclinical studies. A solid dosage form was manufactured to improve the bioavailability properties. In the current study, we sought to evaluate the oral preclinical toxicity of the MIX–160 dosage form, which showed no mortality or significant changes in the body weight, food consumption and tissue/organ mass in rats. Three daily oral doses (50, 300 and 2000 mg/kg of MIX–160) were assayed for 28 days. The results showed no structural abnormalities in the histological analysis and no significant changes (p > 0.05) in the liver biochemical markers (total bilirubin, AST and ALT) compared to the control group. The above findings showed that the MIX–160 dosage form did not exhibit relevant toxic effects, which suggests its potential safety as a drug candidate for clinical studies. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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11 pages, 2226 KiB

Open AccessArticle

Compounding in Ukraine: Assessment of the Risks for the Ointment’s Quality by the FMECA Method

by Lesia Savchenko, Yuri Pidpruzhnykov, Roman Lesyk, Liudas Ivanauskas, Alla Kotvitska and Victoriya Georgiyants

Sci. Pharm. 2022, 90(2), 25; https://doi.org/10.3390/scipharm90020025 - 19 Apr 2022

Cited by 1 | Viewed by 3274

Abstract

The level of compounded medicines (CM) quality has always been questioned in different countries. This problem has been resolved by the introduction of quality assurance system (QAS) standards. One of its main areas of significance is the risks assessment process, which is especially [...] Read more.

The level of compounded medicines (CM) quality has always been questioned in different countries. This problem has been resolved by the introduction of quality assurance system (QAS) standards. One of its main areas of significance is the risks assessment process, which is especially important for the compounding pharmacy according to the requirements of different international documents. Since ointments constitute a large part of CM, quantity assessment of risks for their quality by the FMECA method has been completed. During the first step of the research, 42 potential deviations of compounded ointments (CO) quality were identified. Via the questioning of compounding pharmacies specialists in different regions of Ukraine by a pre-developed ten-point scale, the severity of deviations consequence, their occurrence probability, and detecting possibility were determined followed by the calculation of the priority risk number (PRN) value. The Pareto analysis showed that nine possible CO quality defects represented 21% of their total number. Defects related to the composition or technology of ointments (29%) and their compliance with microbiological purity requirements (23%) had the largest percentage contribution to the total PRN value. It was also found that the deviations consequence had the most serious impact on the CO quality, due to their direct influence on patient health. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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24 pages, 3851 KiB

Open AccessArticle

Repurposing of Four Drugs as Anti-SARS-CoV-2 Agents and Their Interactions with Protein Targets

by Luis C. Vesga, Camilo A. Ruiz-Hernández, Jeimmy J. Alvarez-Jacome, Jonny E. Duque, Bladimiro Rincon-Orozco and Stelia C. Mendez-Sanchez

Sci. Pharm. 2022, 90(2), 24; https://doi.org/10.3390/scipharm90020024 - 14 Apr 2022

Cited by 6 | Viewed by 4701

Abstract

Although there are existing vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), new COVID-19 cases are increasing due to low immunization coverage and the emergence of new variants. For this reason, new drugs to treat and prevent severe COVID-19 are needed. Here, we [...] Read more.

Although there are existing vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), new COVID-19 cases are increasing due to low immunization coverage and the emergence of new variants. For this reason, new drugs to treat and prevent severe COVID-19 are needed. Here, we provide four different FDA-approved drugs against SARS-CoV-2 proteins involved in the entry and replication process, aiming to identify potential drugs to treat COVID-19. We use the main protease (M^pro), the spike glycoprotein (S protein), and RNA-dependent RNA polymerase (RdRp) as protein targets for anti- SARS-CoV-2 drugs. In our constructed database, we selected different drugs against each target (M^pro, S protein, and RdRp) based on their common interactions with relevant residues involved in viral entry at the host cell and replication. Furthermore, their stability inside the binding pocket, as well as their predicted binding-free energy, allow us to provide new insight into the possible drug repurposing of viomycin (interacting with M^pro) due to its interactions with key residues, such as Asn 143, Glu 166, and Gln 189 at the same time as hesperidin (interacting with the S protein) is interacting with residues Tyr 449, Ser 494, and Thr 500, keeping inside the predicted binding pocket, as well as interacting with residues in different variants of concern. Finally, we also suggest nystatin and elvitegravir (interacting with RdRp) as possible drugs due to their stability within the predicted pocket along the simulation and their interaction with key residues, such as Asp 760, Asp 761, and Asp 618. Altogether our results provide new knowledge about the possible mechanism of the inhibition of viomycin, hesperidin, elvitegravir, and nystatin to inhibit the viral life cycle of SARS-CoV-2 and some of its variants of concern (VOC). Additionally, some iodide-based contrast agents were also found to bind the S protein strongly, i.e., iohexol (−58.99 Kcal/mol), iotrolan (−76.19 Kcal/mol), and ioxilan (−62.37 Kcal/mol). Despite the information we report here as the possible strong interaction between these contrast agents and the SARS-CoV-2′s S protein, M^pro, and RdRp, we believe that further investigation, including chemical modifications in their structures, are needed for COVID-19 treatment. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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18 pages, 32993 KiB

Open AccessArticle

Antineoplastic Activity of Water-Soluble Form of Novel Kinase Inhibitor 1-(4-Chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione immobilized on Polymeric Poly(PEGMA-co-DMM) Carrier

by Nataliya Finiuk, Olga Klyuchivska, Nataliya Mitina, Halyna Kuznietsova, Kateryna Volianiuk, Alexander Zaichenko, Volodymyr Rybalchenko and Rostyslav Stoika

Sci. Pharm. 2022, 90(1), 7; https://doi.org/10.3390/scipharm90010007 - 21 Jan 2022

Viewed by 3675

Abstract

The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by its poor water solubility. In this study, the mechanisms of the antineoplastic action of MI-1 and its MI-1/M5 complex with M5 carrier [...] Read more.

The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by its poor water solubility. In this study, the mechanisms of the antineoplastic action of MI-1 and its MI-1/M5 complex with M5 carrier (poly (PEGMA-co-DMM)) towards human colon carcinoma HCT116 cells were investigated by using the MTT and clonogenic assays, DNA intercalation with methyl green replacement, alkaline DNA comet assay, and Western-blot analysis. MI-1 compound and its MI-1/M5 complex possessed high toxicity towards colon (HCT116), cervical (HeLa) carcinoma cells and melanoma (SK-MEL-28) cells with GI₅₀ value in a range of 0.75–7.22 µg/mL, and demonstrated high selectivity index (SI ˃ 6.9). The p53 status of colon cancer cells did not affect the sensitivity of these cells to the treatment with MI-1 and its MI-1/M5 complex. M5 polymer possessed low toxicity towards studied cells. The MI-1, MI-1/M5, and M5 only slightly inhibited growth of the pseudo-normal HaCaT and Balb/c 3T3 cell lines (GI₅₀ ˃ 50 μg/mL). The MI-1 and its MI-1/M5 complex induced mitochondria-dependent pathway of apoptosis, damage of the DNA, and morphological changes in HCT116 cells, and affected the G2/M transition checkpoint. The MI-1 intercalated into the DNA molecule, while such capability of MI-1/M5 complex and M5 polymer was much lower. Thus, poly (PEGMA-co-DMM) might be a promising carrier for delivery of the maleimide derivative, MI-1, a novel kinase inhibitor, through improving its solubility in aqueous media and enhancing its antiproliferative action towards human tumor cells. Studies are in progress on the treatment of Nemeth-Kellner lymphoma (NK/Ly)-bearing mice with the MI-1 and MI-1/M5 complex. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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8 pages, 1530 KiB

Open AccessArticle

A New Practice to Monitor the Fabrication Process of Fab-Targeting Ligands from Bevacizumab by LC-MS: Preparation and Analytical Characterization

by Franck Marquet, Valentina D’Atri, Davy Guillarme and Gerrit Borchard

Sci. Pharm. 2022, 90(1), 5; https://doi.org/10.3390/scipharm90010005 - 4 Jan 2022

Cited by 3 | Viewed by 4790

Abstract

The objective of this study was to qualitatively evaluate a Fab-targeting ligand preparation containing free thiol groups in the hinge region by using bevacizumab as a model. The evaluation focused on the purification of fragments through a nonaffinity-based process using a centrifugal ultrafiltration [...] Read more.

The objective of this study was to qualitatively evaluate a Fab-targeting ligand preparation containing free thiol groups in the hinge region by using bevacizumab as a model. The evaluation focused on the purification of fragments through a nonaffinity-based process using a centrifugal ultrafiltration technique and mild reduction conditions for the intact production of F(ab’) fragments with specific inter-heavy-chain disulfide bonds cleavage. Under these conditions, F(ab’) fragments with a defined chemical composition were successfully obtained via proteolytic digestion followed by a controlled reduction reaction process maintaining the integrity of the binding sites. The ultrafiltration purification technique appears to be suitable for the removal of the digestive enzyme but inefficient for the removal of Fc fragments, thus requiring additional processing. A suitable analytical strategy was developed, allowing us to demonstrate the reformation of disulfide bridges between the two reduced cysteines within F(ab’) fragments. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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8 pages, 806 KiB

Open AccessCommunication

Compatibility of Different Formulations in Pentravan^® and Pentravan^® Plus for Transdermal Drug Delivery

by Hudson Polonini, Sarah Taylor and Clark Zander

Sci. Pharm. 2021, 89(4), 51; https://doi.org/10.3390/scipharm89040051 - 23 Nov 2021

Cited by 2 | Viewed by 3710

Abstract

The potential therapeutic benefit of transdermal delivery systems for some active pharmaceutical ingredients (APIs) has been well-established for decades within the scientific community. However, together with the clinical efficacy, there is the need for an evaluation of the stability of such APIs in [...] Read more.

The potential therapeutic benefit of transdermal delivery systems for some active pharmaceutical ingredients (APIs) has been well-established for decades within the scientific community. However, together with the clinical efficacy, there is the need for an evaluation of the stability of such APIs in bases with known transdermal capabilities, which is necessary to provide the compounding pharmacist with confidence when providing transdermal products. In this study, the stability of danazol, metformin HCl, and resveratrol as individual ingredients, as well as metformin HCl, resveratrol, and Vitamin D3 in combinations at bracketed high and low concentrations, were evaluated over a period of 6 months, using a ready-to-use transdermal vehicle for compounding pharmacies (Pentravan^® or Pentravan^® Plus). The five formulations tested (F1: Danazol 50 mg/g + Miodesin^TM 85 mg/g in Pentravan^®, F2: Metformin HCl 200 mg/g in Pentravan^®, F3: Resveratrol 200 mg/g in Pentravan^®, F4: Metformin HCl 100 mg/g + Resveratrol 100 mg/g + Vitamin D3 5000 IU in Pentravan^®, and F5: Metformin HCl 200 mg/g + Resveratrol 200 mg/g + Vitamin D3 5000 IU in Pentravan^® Plus) presented a beyond-use date of at least 6 months, presenting high convenience for the compounding pharmacies. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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21 pages, 23182 KiB

Open AccessArticle

Computer-Aided Design of Peptidomimetic Inhibitors of Falcipain-3: QSAR and Pharmacophore Models

by Boris D. Bekono, Akori E. Esmel, Brice Dali, Fidele Ntie-Kang, Melalie Keita, Luc C. O. Owono and Eugene Megnassan

Sci. Pharm. 2021, 89(4), 44; https://doi.org/10.3390/scipharm89040044 - 29 Sep 2021

Cited by 5 | Viewed by 3619

Abstract

In this work, antiparasitic peptidomimetics inhibitors (PEP) of falcipain-3 (FP3) of Plasmodium falciparum (Pf) are proposed using structure-based and computer-aided molecular design. Beginning with the crystal structure of PfFP3-K11017 complex (PDB ID: 3BWK), three-dimensional (3D) models of FP3-PEPx complexes with [...] Read more.

In this work, antiparasitic peptidomimetics inhibitors (PEP) of falcipain-3 (FP3) of Plasmodium falciparum (Pf) are proposed using structure-based and computer-aided molecular design. Beginning with the crystal structure of PfFP3-K11017 complex (PDB ID: 3BWK), three-dimensional (3D) models of FP3-PEPx complexes with known activities (

{IC}_{50}^{\exp}

) were prepared by in situ modification, based on molecular mechanics and implicit solvation to compute Gibbs free energies (GFE) of inhibitor-FP3 complex formation. This resulted in a quantitative structure–activity relationships (QSAR) model based on a linear correlation between computed GFE (ΔΔG_com) and the experimentally measured

{IC}_{50}^{\exp}

. Apart from the structure-based relationship, a ligand-based quantitative pharmacophore model (PH4) of novel PEP analogues where substitutions were directed by comparative analysis of the active site interactions was derived using the proposed bound conformations of the PEPx. This provided structural information useful for the design of virtual combinatorial libraries (VL), which was virtually screened based on the 3D-QSAR PH4. The end results were predictive inhibitory activities falling within the low nanomolar concentration range. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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18 pages, 1770 KiB

Open AccessArticle

A Comprehensive Spectroscopic Analysis of the Ibuprofen Binding with Human Serum Albumin, Part II

by Anna Ploch-Jankowska, Danuta Pentak and Jacek E. Nycz

Sci. Pharm. 2021, 89(3), 30; https://doi.org/10.3390/scipharm89030030 - 22 Jun 2021

Cited by 9 | Viewed by 6307

Abstract

Human serum albumin (HSA) is the most abundant human plasma protein. HSA plays a crucial role in many binding endos- and exogenous substances, which affects their pharmacological effect. The innovative aspect of the study is not only the interaction of fatted (HSA) and [...] Read more.

Human serum albumin (HSA) is the most abundant human plasma protein. HSA plays a crucial role in many binding endos- and exogenous substances, which affects their pharmacological effect. The innovative aspect of the study is not only the interaction of fatted (HSA) and defatted (dHSA) human serum albumin with ibuprofen (IBU), but the analysis of the influence of temperature on the structural modifications of albumin and the interaction between the drug and proteins from the temperature characteristic of near hypothermia (308 K) to the temperature reflecting inflammation in the body (312 K and 314 K). Ibuprofen is a non-steroidal anti-inflammatory drug. IBU is used to relieve acute pain, inflammation, and fever. To determine ibuprofen’s binding site in the tertiary structure of HSA and dHSA, fluorescence spectroscopy was used. On its basis, the fluorescent emissive spectra of albumin (5 × 10⁻⁶ mol/dm³) without and with the presence of ibuprofen (1 × 10⁻⁵–1 × 10⁻⁴ mol/dm³) was recorded. The IBU-HSA complex’s fluorescence was excited by radiation of wavelengths of λ_ex 275 nm and λ_ex 295 nm. Spectrophotometric spectroscopy allowed for recording the absorbance spectra (zero-order and second derivative absorption spectra) of HSA and dHSA under the influence of ibuprofen (1 × 10⁻⁴ mol/dm³). To characterize the changes of albumin structure the presence of IBU, circular dichroism was used. The data obtained show that the presence of fatty acids and human serum albumin temperature influences the strength and type of interaction between serum albumin and drug. Ibuprofen binds more strongly to defatted human serum albumin than to albumin in the presence of fatty acids. Additionally, stronger complexes are formed with increasing temperatures. The competitive binding of ibuprofen and fatty acids to albumin may influence the concentration of free drug fraction and thus its therapeutic effect. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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17 pages, 1093 KiB

Open AccessArticle

Characterization of Phytochemical Components of Crocus sativus Leaves: A New Attractive By-Product

by Olha Mykhailenko, Liudas Ivanauskas, Ivan Bezruk, Lyudmila Sidorenko, Roman Lesyk and Victoriya Georgiyants

Sci. Pharm. 2021, 89(2), 28; https://doi.org/10.3390/scipharm89020028 - 15 Jun 2021

Cited by 18 | Viewed by 6655

Abstract

Crocus sativus L. is one of the world’s most famous saffron production crops and its enormous by-products, such as leaves, are an excellent source of bioactive compounds with potential nutritional applications. The total phenolic content of Crocus leaves was 5.44 ± 0.01 mg [...] Read more.

Crocus sativus L. is one of the world’s most famous saffron production crops and its enormous by-products, such as leaves, are an excellent source of bioactive compounds with potential nutritional applications. The total phenolic content of Crocus leaves was 5.44 ± 0.01 mg GAE/g, and the total flavonoid content was 2.63 ± 0.05 mg RE/g, respectively. The main bioactive compounds in the leaves, such as polyphenols, flavonoids by HPLC and carboxylic acids, and amino acids, were also identified by GC-MS. HPLC analyses revealed mangiferin as a dominant constituent (1.26 ± 0.02 mg/g). C. sativus contains seven essential amino acids (ILE, LEU, LYS, MET, PHE, THR, TRP, VAL) in high concentration. Among them, isoleucine (7965 µg/g) was the dominant compound. In addition, the K and Ca concentrations in the leaves were significant (p < 0.05). The chemical composition revealed α-linolenic acid (22,490 µg/g) and linoelaidic acid (9880 µg/g) to be major constituents among all the acids found in the Crocus leaves. The extracts of C. sativus leaves showed the highest inhibitory activity for Gram-positive (B. subtilis and S. aureus) bacteria in the in vitro assay. The current results identify and underline the potential of natural products from C. sativus leaves that can add value to saffron production. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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8 pages, 2940 KiB

Open AccessArticle

Antihyperuricemic, Anti-Inflammatory and Antihypertensive Effect of a Dry Extract from Solidago virgaurea L. (Asteraceae)

by Mircea Tămaş, Oliviu Vostinaru, Loredana Soran, Ildiko Lung, Ocsana Opris, Anca Toiu, Alexandru Gavan, Elena Dinte and Cristina Mogosan

Sci. Pharm. 2021, 89(2), 27; https://doi.org/10.3390/scipharm89020027 - 14 Jun 2021

Cited by 10 | Viewed by 5443

Abstract

Solidago virgaurea L. is a perennial plant used in European traditional medicine as a diuretic or a remedy for inflammatory conditions of the urinary tract but also for gout, especially in the Balkans. The present study was focused on a preclinical, in vivo [...] Read more.

Solidago virgaurea L. is a perennial plant used in European traditional medicine as a diuretic or a remedy for inflammatory conditions of the urinary tract but also for gout, especially in the Balkans. The present study was focused on a preclinical, in vivo evaluation of antihyperuricemic, anti-inflammatory, and antihypertensive effects of a dry extract from S. virgaurea L. (ESV). Colorimetric and HPLC–MS techniques were used to identify the main chemical constituents of ESV. Antihyperuricemic effect of ESV was assessed in a rat model of hyperuricemia induced by the administration of potassium oxonate. Antihypertensive effect of ESV was evaluated in hyperuricemic rats by monitoring systolic blood pressure with a non-invasive blood-pressure recording system. The anti-inflammatory effect of ESV was tested using a rat model of paw edema. The main chemical constituents of ESV were rutin and phenolic acids represented by chlorogenic and caffeic acid. ESV demonstrated significant antihyperuricemic effects in rats due to an uricosuric mechanism. Additionally, ESV reduced the progression of arterial hypertension in hyperuricemic rats and also showed anti-inflammatory properties slightly inferior to diclofenac. The results suggest that ESV could be a natural remedy for the treatment of gout and protection against endothelial dysfunction caused by hyperuricemia. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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Review

Jump to: Research

16 pages, 336 KiB

Open AccessReview

Wide Use of Hyaluronic Acid in the Process of Wound Healing—A Rapid Review

by Magdalena Antoszewska, Ewa Maria Sokolewicz and Wioletta Barańska-Rybak

Sci. Pharm. 2024, 92(2), 23; https://doi.org/10.3390/scipharm92020023 - 25 Apr 2024

Cited by 2 | Viewed by 7011

Abstract

Hyaluronic acid (HA), as one of the main components of the extracellular matrix (ECM), plays an important role in the process of wound-healing and tissue-repair processes due to its unique properties and different physiological functions. HA has an ability to maintain a moist [...] Read more.

Hyaluronic acid (HA), as one of the main components of the extracellular matrix (ECM), plays an important role in the process of wound-healing and tissue-repair processes due to its unique properties and different physiological functions. HA has an ability to maintain a moist environment that promotes healing, the stimulation of growth factors and cellular constituents, and the migration of various cells essential for healing. This paper offers a review of HA use in the process of wound healing, with emphasis on hard-to-heal wounds, and examines its various applications in ophthalmology and otorhinolaryngology. It proves HA to be a versatile agent which finds its use in various fields of medicine for its antioxidant, anti-inflammatory, antibacterial properties and accelerated wound healing. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

17 pages, 1730 KiB

Open AccessReview

Complementary Practices in Pharmacy and Their Relation to Glaucoma—Classification, Definitions, and Limitations

by Tibor Rák and Adrienne Csutak

Sci. Pharm. 2024, 92(1), 16; https://doi.org/10.3390/scipharm92010016 - 14 Mar 2024

Cited by 2 | Viewed by 2957

Abstract

Background: Traditional and evidence-based medicines, as seen depicted throughout human history, reportedly first begin with the application of medicinal plants, animal products, or inorganic minerals as a basic framework towards effectively engineering the prototypes generally aligned to pharmaceuticals and medical nutrition. The growing [...] Read more.

Background: Traditional and evidence-based medicines, as seen depicted throughout human history, reportedly first begin with the application of medicinal plants, animal products, or inorganic minerals as a basic framework towards effectively engineering the prototypes generally aligned to pharmaceuticals and medical nutrition. The growing global trend of complementary treatments for glaucoma can be explained by the intraocular pressure (IOP)-independent mechanisms of the disease and its interpretation as a progressive neurodegenerative disorder. Unfortunately, the categorical positions of the major fields of applied popular complementary therapies and their relation to glaucoma are consistently neglected. Methods: In consideration of bibliographic resources, the most well-known online scientific databases were searched. Conclusion: The rising popularity and the trends of products coming onto the market cannot escape the attention of pharmacists and ophthalmologists, as their patients suffering from eye diseases are also increasingly looking for such medicinal products. Most of them still lack knowledge of the appropriate evidence and side effect profiles. Our proposed systematic charts demonstrate the position of each mainstream complementary therapy throughout the applied medical sciences and are distinctively unique; we could not find any similar relevant illustration or resource among the published international literature. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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19 pages, 1632 KiB

Open AccessReview

In Vitro and Ex Vivo Models for Screening Topical Anti-Inflammatory Drugs

by Juan Luis Pérez-Salas, Martha Rocío Moreno-Jiménez, Nuria Elizabeth Rocha-Guzmán, Rubén Francisco González-Laredo, Luis Medina-Torres and José Alberto Gallegos-Infante

Sci. Pharm. 2023, 91(2), 20; https://doi.org/10.3390/scipharm91020020 - 17 Apr 2023

Cited by 10 | Viewed by 11908

Abstract

Skin inflammation occurs as an immune response to various stimuli such as ultraviolet light, irritants, or any type of skin barrier injury. Finding safe and effective drugs to combat skin inflammation remains a research challenge. Ethical and legal considerations in animal testing encourage [...] Read more.

Skin inflammation occurs as an immune response to various stimuli such as ultraviolet light, irritants, or any type of skin barrier injury. Finding safe and effective drugs to combat skin inflammation remains a research challenge. Ethical and legal considerations in animal testing encourage the development of in vitro and ex vivo models for the detection of skin inflammation. This report presents an updated review of non-animal study models available for screening drugs with anti-inflammatory potential. It includes a description of the basic methods used to inhibit protein denaturation and red blood cell membrane stability. Three in vitro inhibition assay methods for enzymes relevant to the skin inflammatory process are then described. The development of cell culture models is described: relatively simple and easy-to-produce two-dimensional (2D) skin cell cultures that allow assessment of response to a given stimulus, three-dimensional (3D) cell cultures that better mimic human skin physiology by more accurately replicating mechanical and chemical signals, and vascularized 3D skin models with dynamic perfusion and microfluidic devices known as skin on a chip. Finally, ex vivo skin models are presented that could more accurately represent human skin in terms of structure, cell signaling mechanisms, and absorption effects. Although the current development of models without the use of animals is promising, improvements and refinements are needed to make the models more suitable as screening platforms for topical anti-inflammatory drugs. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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34 pages, 10916 KiB

Open AccessReview

Medicinal Chemistry of Quinazolines as Anticancer Agents Targeting Tyrosine Kinases

by Mohamed F. Zayed

Sci. Pharm. 2023, 91(2), 18; https://doi.org/10.3390/scipharm91020018 - 28 Mar 2023

Cited by 16 | Viewed by 6316

Abstract

Cancer is a large group of diseases that can affect any organ or body tissue due to the abnormal cellular growth with the unknown reasons. Many of the existing chemotherapeutic agents are highly toxic with a low level of selectivity. Additionally, they lead [...] Read more.

Cancer is a large group of diseases that can affect any organ or body tissue due to the abnormal cellular growth with the unknown reasons. Many of the existing chemotherapeutic agents are highly toxic with a low level of selectivity. Additionally, they lead to development of therapeutic resistance. Hence, the development of targeted chemotherapeutic agents with low side effects and high selectivity is required for cancer treatment. Quinazoline is a vital scaffold well-known to be linked with several biological activities. The anticancer activity is one of the prominent biological activities of this scaffold. Several established anticancer quinazolines work by different mechanisms on the various molecular targets. The aim of this review is to present different features of medicinal chemistry as drug design, structure activity relationship, and mode of action of some targeted anticancer quinazoline derivatives. It gives comprehensive attention on the chemotherapeutic activity of quinazolines in the viewpoint of drug discovery and its development. This review provides panoramic view to the medicinal chemists for supporting their efforts to design and synthesize novel quinazolines as targeted chemotherapeutic agents. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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10 pages, 1378 KiB

Open AccessReview

Effectiveness of Platelet-Rich Plasma in the Treatment of Androgenic Alopecia Compared to Placebo and Topical Minoxidil: A Systematic Review

by Julia Maria Borowiecka, Bartosz Dalewski and Łukasz Pałka

Sci. Pharm. 2023, 91(1), 4; https://doi.org/10.3390/scipharm91010004 - 31 Dec 2022

Cited by 1 | Viewed by 10388

Abstract

Platelet-rich plasma (PRP) has become an increasingly popular alternative or additional method in treating androgenic alopecia (AGA). AGA is a multifactorial disease, in which testosterone plays a significant role in influencing hair growth. The aim of this study was to evaluate the effectiveness [...] Read more.

Platelet-rich plasma (PRP) has become an increasingly popular alternative or additional method in treating androgenic alopecia (AGA). AGA is a multifactorial disease, in which testosterone plays a significant role in influencing hair growth. The aim of this study was to evaluate the effectiveness of PRP treatment in AGA affecting men and women. The research was performed using the following databases: PubMed, Embase, and Cochrane Library. The effects were measured with a TrichoScan by comparing the initial and final hair density. A significant difference was observed between the areas of the scalp where PRP injections were made and those where saline was administered. Compared to conventional minoxidil 5% topical PRP, PRP is more effective in treating alopecia. A beneficial outcome of combined therapy with PRP and minoxidil 5% was observed. Therefore, PRP is not only an excellent alternative for patients in whom the minoxidil 5% topical monotherapy did not bring the expected effects or who experienced unacceptable side effects, but can also be used as a complementary therapy. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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11 pages, 804 KiB

Open AccessReview

Melt Fusion Techniques for Solubility Enhancement: A Comparison of Hot Melt Extrusion and KinetiSol^® Technologies

by Srinivas Ajjarapu, Srikanth Banda, Pratap Basim and Narendar Dudhipala

Sci. Pharm. 2022, 90(3), 51; https://doi.org/10.3390/scipharm90030051 - 24 Aug 2022

Cited by 7 | Viewed by 4817

Abstract

A successful candidate for oral drug delivery needs to possess adequate solubility and dissolution rate to elicit its therapeutic action. Extensive research is being carried out to enhance the solubility of poorly soluble drugs through a number of techniques involving polymeric and non-polymeric [...] Read more.

A successful candidate for oral drug delivery needs to possess adequate solubility and dissolution rate to elicit its therapeutic action. Extensive research is being carried out to enhance the solubility of poorly soluble drugs through a number of techniques involving polymeric and non-polymeric approaches. Non-polymeric approaches such as micronization and nanocrystals are successful in improving the apparent solubility of drugs, but the sustenance of solubility is not always possible. Amorphous solid dispersions (ASDs) lead to solubility enhancement as well as the maintenance of solubility with the assistance of polymers, thereby improving bioavailability. Spray drying, hot melt extrusion (HME), and KinetiSol^® technologies are some of the techniques capable of manufacturing ASDs. Each of these techniques has its own advantages and disadvantages in terms of processing challenges and applicability in preparing ASDs. The latter two technologies are similar in being fusion and non-solvent techniques to improve solubility. This review compares both HME and KinetiSol^® techniques regarding mechanism, equipment design, formulation, and process parameters involved and scalability. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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25 pages, 23874 KiB

Open AccessReview

Systematic Review on the Effectiveness of Essential and Carrier Oils as Skin Penetration Enhancers in Pharmaceutical Formulations

by Bahjat Alhasso, Muhammad Usman Ghori and Barbara R. Conway

Sci. Pharm. 2022, 90(1), 14; https://doi.org/10.3390/scipharm90010014 - 19 Feb 2022

Cited by 29 | Viewed by 14739

Abstract

Oils, including essential oils and their constituents, are widely reported to have penetration enhancement activity and have been incorporated into a wide range of pharmaceutical formulations. This study sought to determine if there is an evidence base for the selection of appropriate oils [...] Read more.

Oils, including essential oils and their constituents, are widely reported to have penetration enhancement activity and have been incorporated into a wide range of pharmaceutical formulations. This study sought to determine if there is an evidence base for the selection of appropriate oils for particular applications and compare their effectiveness across different formulation types. A systematic review of the data sources, consisting of Google Scholar, EMBASE, PubMed, Medline, and Scopus, was carried out and, following screening and quality assessment, 112 articles were included within the analysis. The research was classified according to the active pharmaceutical ingredient, dosage form, in vitro/in vivo study, carrier material(s), penetration enhancers as essential oils, and other chemical enhancers. The review identified four groups of oils used in the formulation of skin preparations; in order of popularity, these are terpene-type essential oils (63%), fatty acid-containing essential oils (29%) and, finally, 8% of essential oils comprising Vitamin E derivatives and miscellaneous essential oils. It was concluded that terpene essential oils may have benefits over the fatty acid-containing oils, and their incorporation into advanced pharmaceutical formulations such as nanoemulsions, microemulsions, vesicular systems, and transdermal patches makes them an attractive proposition to enhance drug permeation through the skin. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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11 pages, 359 KiB

Open AccessReview

Traditional Uses, Phytochemistry, and Pharmacology of Elegia Species: A Review

by Panagiotis Lymperis, Ekaterina-Michaela Tomou, Marco Nuno De Canha, Namrita Lall and Helen Skaltsa

Sci. Pharm. 2022, 90(1), 4; https://doi.org/10.3390/scipharm90010004 - 27 Dec 2021

Cited by 3 | Viewed by 3825

Abstract

In South Africa, plants belonging to the Restionaceae family possess an ecological dominance. As a result, they have been the subject of numerous morphological, anatomical, and evolutionary studies. However, few studies have focused on their phytochemical profile and their potential pharmacological activities. The [...] Read more.

In South Africa, plants belonging to the Restionaceae family possess an ecological dominance. As a result, they have been the subject of numerous morphological, anatomical, and evolutionary studies. However, few studies have focused on their phytochemical profile and their potential pharmacological activities. The genus Elegia L. is the second largest of this family comprising 52 species, which are mainly used as materials for thatching. Limited studies on the chemical constituents of Elegia species and their importance as medicinal plants have been undertaken. This review provides constructive and extensive information about the botanical characterization, distribution, traditional uses, phytochemistry and pharmacology of the genus Elegia. A comprehensive search of previously published literature was performed for studies on this genus, using databases with different key search words. This survey documented 52 Elegia species summarizing their previous taxonomic classification. In addition, 14 species were found to be studied for their phytochemical profile, revealing 14 chemical compounds. Concerning their biological activities, only one species (E. tectorum (L.f.) Moline and H.P.Linder) is reported for its anti-wrinkle activity. Moreover, two species are locally used for thatching and as materials for brooms. The present review highlights the Elegia genus as an important source of bioactive phytochemicals with flavonol glycosides being the main metabolites and reveals the uncharted territory of this genus for new research studies. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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Using Metabolite Data to Develop Patient Centric Specification for Amide Impurity in Vildagliptin Tablets

by Naseem Ahmad Charoo, Syeed Untoo and Ziyaur Rahman

Sci. Pharm. 2022, 90(1), 1; https://doi.org/10.3390/scipharm90010001 - 22 Dec 2021

Cited by 4 | Viewed by 4561

Abstract

Many specified impurities in vildagliptin’s finished product have been disclosed in the literature that are above their qualification threshold. We used the impurity B (amide impurity) as a case example to explore whether existing literature can be leveraged to determine the safe level [...] Read more.

Many specified impurities in vildagliptin’s finished product have been disclosed in the literature that are above their qualification threshold. We used the impurity B (amide impurity) as a case example to explore whether existing literature can be leveraged to determine the safe level of impurity and thereby develop a patient-centric specification (PCS) for impurities. No-observed-adverse-effect level (NOAEL) was derived from rate metabolism information and converted to human equivalent dose (HED). The HED was estimated as 6.5 mg/day. The high qualification levels are supported by repeat dose toxicity studies performed in rats, mice and dogs. Maximum theoretical amount (MTA) was correlated with the maximum observed amount (MOA) to verify whether the exposure was due to impurity and/or metabolite. MOA/MTA was found ≥1 suggesting that metabolism contributed to the amount excreted in feces and therefore could be used to further justify a higher specification limit than the usual one of ≤0.5%. Quite often the drug metabolism and degradation pathways overlap, resulting in the formation of identical constituents. Therefore, metabolism data can be leveraged for deriving safe levels of degradation impurities and develop PCS for impurities. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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36 pages, 4121 KiB

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Phytochemistry and Evidence-Based Traditional Uses of the Genus Achillea L.: An Update (2011–2021)

by Christina Barda, Maria-Eleni Grafakou, Ekaterina-Michaela Tomou and Helen Skaltsa

Sci. Pharm. 2021, 89(4), 50; https://doi.org/10.3390/scipharm89040050 - 22 Nov 2021

Cited by 21 | Viewed by 5707

Abstract

Knowledge within the field of phytochemistry research has accelerated at a tremendous speed. The excess of literature reports featuring plants of high ethnopharmacological importance, in combination with our interest in the Asteraceae family and traditional medicine, led us to acknowledge the value of [...] Read more.

Knowledge within the field of phytochemistry research has accelerated at a tremendous speed. The excess of literature reports featuring plants of high ethnopharmacological importance, in combination with our interest in the Asteraceae family and traditional medicine, led us to acknowledge the value of the Achillea L. genus. In a broad context, the various Achillea species are used around the globe for the prevention and treatment of different diseases, including gastrointestinal problems, haemorrhages, pneumonia, rheumatic pains, diuresis, inflammation, infections, and wounds, as well as menstrual and gynaecologic abnormalities. The present review aims to provide and summarize the recent literature (2011–2021) on the phytochemistry of the Achillea genus. In parallel, this study attempts to bridge the reports on the traditional uses with modern pharmacological data. Research articles that focused on secondary metabolites, traditional uses and pharmacological activities were collected from various scientific databases such as Pubmed, ScienceDirect, Reaxys and Google Scholar. This study revealed the presence of 141 phytochemicals, while 24 traditionally used Achillea spp. were discussed in comparison to current data with an experimental basis. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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16 pages, 1005 KiB

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New Frontiers on Adjuvants Drug Strategies and Treatments in Periodontitis

by Gaetano Isola, Alessandro Polizzi, Simona Santonocito, Domenico Dalessandri, Marco Migliorati and Francesco Indelicato

Sci. Pharm. 2021, 89(4), 46; https://doi.org/10.3390/scipharm89040046 - 22 Oct 2021

Cited by 13 | Viewed by 7173

Abstract

Causes of the progression of periodontitis such as an imbalance between the immune response by the host by the release of inflammatory mediators in the response of the oral pathogenic dysbiotic biofilm have been identified. New insights on specific cell signaling pathways that [...] Read more.

Causes of the progression of periodontitis such as an imbalance between the immune response by the host by the release of inflammatory mediators in the response of the oral pathogenic dysbiotic biofilm have been identified. New insights on specific cell signaling pathways that appear during periodontitis have attracted the attention of researchers in the study of new personalised approaches for the treatment of periodontitis. The gold standard of non-surgical therapy of periodontitis involves the removal of supra and subgingival biofilm through professional scaling and root planing (SRP) and oral hygiene instructions. In order to improve periodontal clinical outcomes and overcome the limitations of traditional SRP, additional adjuvants have been developed in recent decades, including local or systemic antibiotics, antiseptics, probiotics, anti-inflammatory and anti-resorptive drugs and host modulation therapies. This review is aimed to update the current and recent evolution of therapies of management of periodontitis based on the adjunctive and target therapies. Moreover, we discuss the advances in host modulation of periodontitis and the impact of targeting epigenetic mechanisms approaches for a personalised therapeutic success in the management of periodontitis. In conclusion, the future goal in periodontology will be to combine and personalise the periodontal treatments to the colonising microbial profile and to the specific response of the individual patient. Full article

(This article belongs to the Special Issue Feature Papers in Scientia Pharmaceutica)

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