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Sci. Pharm., Volume 92, Issue 2 (June 2024) – 19 articles

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20 pages, 6550 KiB  
Article
Fluid Dynamics Optimization of Microfluidic Diffusion Systems for Assessment of Transdermal Drug Delivery: An Experimental and Simulation Study
by Dorottya Kocsis, Shanmugam Dhinakaran, Divyam Pandey, András József Laki, Mária Laki, Dániel Sztankovics, Miléna Lengyel, Judit Vrábel, Márton Bese Naszlady, Anna Sebestyén, Jeyaraj Ponmozhi, István Antal and Franciska Erdő
Sci. Pharm. 2024, 92(2), 35; https://doi.org/10.3390/scipharm92020035 - 20 Jun 2024
Viewed by 1412
Abstract
Organ-on-a-chip technologies show exponential growth driven by the need to reduce the number of experimental animals and develop physiologically relevant human models for testing drugs. In vitro, microfluidic devices should be carefully designed and fabricated to provide reliable tools for modeling physiological or [...] Read more.
Organ-on-a-chip technologies show exponential growth driven by the need to reduce the number of experimental animals and develop physiologically relevant human models for testing drugs. In vitro, microfluidic devices should be carefully designed and fabricated to provide reliable tools for modeling physiological or pathological conditions and assessing, for example, drug delivery through biological barriers. The aim of the current study was to optimize the utilization of three existing skin-on-a-chip microfluidic diffusion chambers with various designs. For this, different perfusion flow rates were compared using cellulose acetate membrane, polyester membrane, excised rat skin, and acellular alginate scaffold in the chips. These diffusion platforms were integrated into a single-channel microfluidic diffusion chamber, a multi-channel chamber, and the LiveBox2 system. The experimental results revealed that the 40 µL/min flow rate resulted in the highest diffusion of the hydrophilic model formulation (2% caffeine cream) in each system. The single-channel setup was used for further analysis by computational fluid dynamics simulation. The visualization of shear stress and fluid velocity within the microchannel and the presentation of caffeine progression with the perfusion fluid were consistent with the measured data. These findings contribute to the development and effective application of microfluidic systems for penetration testing. Full article
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20 pages, 2140 KiB  
Article
Fact-Finding Survey and Exploration of Preventive Drugs for Antineoplastic Drug-Induced Oral Mucositis Using the Japanese Adverse Drug Event Report Database
by Hajime Matsuo, Kiri Endo, Hiroyuki Tanaka, Toshihisa Onoda and Toshihiro Ishii
Sci. Pharm. 2024, 92(2), 34; https://doi.org/10.3390/scipharm92020034 - 20 Jun 2024
Viewed by 1377
Abstract
Oral mucositis (OM) is one of the most common adverse events associated with antineoplastic drug treatment. Studies on the risk of antineoplastic drug-induced OM and its prevention are limited. We, therefore, conducted a disproportionality analysis of antineoplastic drug-induced OM and explored candidate preventive [...] Read more.
Oral mucositis (OM) is one of the most common adverse events associated with antineoplastic drug treatment. Studies on the risk of antineoplastic drug-induced OM and its prevention are limited. We, therefore, conducted a disproportionality analysis of antineoplastic drug-induced OM and explored candidate preventive drugs for OM using the Japanese Adverse Drug Event Report (JADER) database. The JADER database showed that between April 2004 and March 2022, antineoplastic drug-related adverse events were reported in 210,822 cases, of which 2922 were OM. Forty-two drugs appeared to be associated with OM. The weibull distribution showed different patterns of time-to-onset depending on the type of antineoplastic drug administered. Cluster analyses classified antineoplastic drugs according to the typical symptoms of OM. These findings suggest that antineoplastic drug-induced OM should be monitored based on expression patterns of symptoms. Upon analyzing the inverse association, several concomitant drugs, including lenalidomide hydrate and febuxostat, were expected to be candidate preventive drugs for antineoplastic drug-induced OM. Concomitant drugs that showed an inverse association with antineoplastic drug-induced OM differed within the Anatomical Therapeutic Chemical classification. These findings could serve as a reference when considering drugs that should be prioritized to validate their prophylactic effect against antineoplastic-induced OM in the future. Full article
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10 pages, 1405 KiB  
Review
Non-Analog Compounds to Sialic Acid as Inhibitors of Influenza Virus Neuraminidase: An Underexplored Approach for Novel Antivirals―Systematic Review
by Luis Márquez-Domínguez, Carolina Jasso-Miranda, Virginia Sedeño-Monge and Gerardo Santos-López
Sci. Pharm. 2024, 92(2), 33; https://doi.org/10.3390/scipharm92020033 - 19 Jun 2024
Viewed by 1447
Abstract
Influenza poses a significant threat to public health worldwide, particularly among vulnerable populations such as children, the elderly, immunocompromised individuals, and those with chronic diseases. It is associated with high mortality and morbidity rates. Neuraminidase inhibitors play a crucial role in influenza treatment [...] Read more.
Influenza poses a significant threat to public health worldwide, particularly among vulnerable populations such as children, the elderly, immunocompromised individuals, and those with chronic diseases. It is associated with high mortality and morbidity rates. Neuraminidase inhibitors play a crucial role in influenza treatment by mitigating the risk of complications and death. However, the genetic variability of the influenza virus enables the emergence of drug-resistant mutations. This review focuses on the search for new compounds that are not analogous to sialic acid, aiming to inhibit the activity of viral neuraminidase in vitro, viral replication in cell cultures, or animal models. Influenza virus strains that have been reported in the literature present specific mutations that generate resistance to neuraminidase inhibitors. Since these inhibitors bear structural resemblance to sialic acid, the predominant location for these mutations is the enzyme’s active site. Consequently, exploring alternative compound classes becomes imperative to circumvent this interaction pattern. These compounds will introduce diverse molecular frameworks, serving as foundational structures for further development through rational drug design, thereby engendering novel antiviral agents targeting influenza. The potential prospects for developing novel influenza antivirals based on these findings are discussed. Full article
(This article belongs to the Topic Challenges and Opportunities in Drug Delivery Research)
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13 pages, 3685 KiB  
Article
Evidence of Hyperglycemic Levels Improving the Binding Capacity between Human Serum Albumin and the Antihypertensive Drug Hydrochlorothiazide
by Marilia Amável Gomes Soares, Franklin Souza-Silva, Carlos Roberto Alves, Leonardo Vazquez, Talita Stelling de Araujo, Carlos Serpa and Otávio Augusto Chaves
Sci. Pharm. 2024, 92(2), 32; https://doi.org/10.3390/scipharm92020032 - 7 Jun 2024
Cited by 5 | Viewed by 1473
Abstract
Cardiovascular diseases (CVDs), especially arterial hypertension, stand as prominent contributors to global mortality. Regrettably, individuals with diabetes encounter a two-fold increase in the risk of mortality associated with CVDs. Hydrochlorothiazide (HCTZ) represents a primary intervention for hypertension, particularly in diabetic patients. Nevertheless, there [...] Read more.
Cardiovascular diseases (CVDs), especially arterial hypertension, stand as prominent contributors to global mortality. Regrettably, individuals with diabetes encounter a two-fold increase in the risk of mortality associated with CVDs. Hydrochlorothiazide (HCTZ) represents a primary intervention for hypertension, particularly in diabetic patients. Nevertheless, there has not yet been a comprehensive assessment of the biophysical characteristics regarding the impact of glucose levels on its binding affinity with human serum albumin (HSA). Thus, the present work reports the interactive profile of HSA/HCTZ in nonglycemic, normoglycemic (80 mg/dL), and hyperglycemic (320 mg/dL) conditions by time-resolved fluorescence, saturation transfer difference–nuclear magnetic resonance (STD-NMR), and surface plasmon resonance (SPR). There was a moderate ground state association of HSA/HCTZ with subdomain IIA that was affected in the presence of different glucose levels. The hyperglycemic condition decreased the binding affinity of HCTZ to subdomain IIA and increased the possibility of subdomain IB also being considered as a secondary binding site due to cooperativity and/or alterations in the protein’s structure. Overall, the glucose level under hyperglycemic conditions led to the cavities being more likely to receive more ligands, offering insights into the necessity of glucose control in the human bloodstream to not impact the residence time (pharmacokinetic profile) and pharmacotherapeutic potential of HCTZ. Full article
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17 pages, 1324 KiB  
Review
Medicinal Use of Chicory (Cichorium intybus L.)
by Łukasz Duda, Karol Kamil Kłosiński, Grażyna Budryn, Andrzej Jaśkiewicz, Damian Kołat, Żaneta Kałuzińska-Kołat and Zbigniew Włodzimierz Pasieka
Sci. Pharm. 2024, 92(2), 31; https://doi.org/10.3390/scipharm92020031 - 5 Jun 2024
Viewed by 2845
Abstract
The aim of this review is to discuss the numerous health-promoting properties of Cichorium intybus L. and bring together a range of publications to broaden knowledge and encourage further research and consideration of the plant use as treatment for a range of conditions. [...] Read more.
The aim of this review is to discuss the numerous health-promoting properties of Cichorium intybus L. and bring together a range of publications to broaden knowledge and encourage further research and consideration of the plant use as treatment for a range of conditions. A comprehensive search of articles in Polish and English from 1986–2022 years was carried out in PubMed, Google Scholar and ScienceDirect using the keywords chicory, Cichorium intybus L., sesquiterpene lactones and their synonyms. Articles were checked for titles, abstracts, and full-text reviews. The first part of the review article discusses chicory, the countries in which it is found, its life cycle or modern cultivation methods, as well as its many uses, which will be discussed in more detail later in the article. The increased interest in plants as medicines or supplements is also briefly mentioned, as well as some limits that are associated with the medical use of plants. In the Results and Discussion section, there is a discussion of the numerous health-promoting properties of Cichorium intybus L. as a whole plant, with its collection of all the components, and we then examine the structure and the individual constituents of Cichorium intybus L. Among these, this article discusses those that can be utilized for causal applications in medicine, including sesquiterpene lactones and polyphenols, mainly known for their anti-cancer properties, although, in this article, their other health-promoting properties are also discussed. The article also examines inulin, a major component of Cichorium intybus L. The Discussion and the Conclusions sections propose directions for more detailed research and the range of factors that may affect specific results, which may have safety implications when used as supplements or medications. Full article
(This article belongs to the Topic Natural Products and Drug Discovery)
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15 pages, 5700 KiB  
Article
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
Viewed by 1136
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  
Article
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
Viewed by 1246
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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35 pages, 6703 KiB  
Review
Drug Delivery Nano-Platforms for Advanced Cancer Therapy
by Ekaterina Naumenko, Ivan Guryanov and Marina Gomzikova
Sci. Pharm. 2024, 92(2), 28; https://doi.org/10.3390/scipharm92020028 - 22 May 2024
Viewed by 1733
Abstract
The incidence of cancer is growing every year and covers all age groups, including the working population, which makes cancer socially significant. Existing methods of treatment, despite the effectiveness of individual compounds in relation to cancer cells, are not perfect due to a [...] Read more.
The incidence of cancer is growing every year and covers all age groups, including the working population, which makes cancer socially significant. Existing methods of treatment, despite the effectiveness of individual compounds in relation to cancer cells, are not perfect due to a number of side effects associated with high doses that physicians are forced to administer when using treatment protocols. A particularly difficult issue is the creation of effective functional containers that would have the properties of targeting certain types of cells. The solution of this problem is currently relevant, which is reflected in the growth of publications on this subject in recent years. The most promising is the use of nanotechnology in the development of bioengineered therapeutics and containers for chemotherapeutic agents. In this review, we tried to assess the trends that exist in this area of research, as well as show the wide using of some commercially available formulations based on the nano-sized vehicles. Full article
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16 pages, 763 KiB  
Article
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 1445
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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11 pages, 1857 KiB  
Article
Advancing Transdermal Delivery by Zn/Ag-Electrode-Printed Iontophoretic Patch with Self-Generating Microcurrents
by Cheng-Liang Peng, Pei-Chi Lee, Hsin-Tung Liu and Ping-Shan Lai
Sci. Pharm. 2024, 92(2), 26; https://doi.org/10.3390/scipharm92020026 - 14 May 2024
Viewed by 1606
Abstract
This study aimed to evaluate Zn/Ag-electrode-printed patches for the transdermal delivery of small molecules through iontophoresis. The Zn/Ag-electrode-printed patches interact with biological liquid electrolytes and generate suitable microcurrents for the iontophoretic delivery of small molecules across the skin. In fluorescein permeation studies, Zn/Ag-electrode-printed [...] Read more.
This study aimed to evaluate Zn/Ag-electrode-printed patches for the transdermal delivery of small molecules through iontophoresis. The Zn/Ag-electrode-printed patches interact with biological liquid electrolytes and generate suitable microcurrents for the iontophoretic delivery of small molecules across the skin. In fluorescein permeation studies, Zn/Ag-electrode-printed patches increased the transdermal depth of fluorescein into the dermis, while the permeation of fluorescein was limited when Zn/C-electrode-printed patches were tested. Further permeation experiments were conducted with 3D skin models, which showed a similar trend to the above, indicating that Zn/Ag-electrode-printed patches had a higher penetration rate compared to the blank. Studies using acetyl hexapeptide-8 as a peptide drug model and sodium ascorbyl phosphate (SAP) as a hydrophilic derivative of ascorbic acid showed that the iontophoretic patch with Zn/Ag electrodes promoted more penetration of drugs than unprinted patches. The permeation of SAP exhibited a two-phase profile with a relatively rapid permeation followed by a sustained, slower permeation. The permeation of acetyl hexapeptide-8 was slower due to its higher molecular weight, but the iontophoretic patch increased the permeation up to 1.5 times more than the unprinted patch. The microcurrent generated by the patch drives the transport of small molecule components through the skin, for the controlled and efficient delivery of therapeutic agents. The flexible design, efficient microcurrent generation, and stable electrodes make the Zn/Ag-electrode-printed patch a promising tool for transdermal drug delivery. Full article
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14 pages, 1859 KiB  
Article
Breast Cancer Prevention by Dietary Polyphenols: Microemulsion Formulation and In Vitro Studies
by Ghea Putri Cristy, Desy Liana, Jaruwan Chatwichien, Chanat Aonbangkhen, Chantragan Srisomsap and Anuchit Phanumartwiwath
Sci. Pharm. 2024, 92(2), 25; https://doi.org/10.3390/scipharm92020025 - 13 May 2024
Viewed by 1620
Abstract
Concerns surrounding breast cancer have been increasing, as it leads to the current global cancer incidence and causes a high mortality rate in women. This study investigated the physiological effects of common dietary polyphenols that might prevent breast cancer progression. Quercetin, kaempferol, and [...] Read more.
Concerns surrounding breast cancer have been increasing, as it leads to the current global cancer incidence and causes a high mortality rate in women. This study investigated the physiological effects of common dietary polyphenols that might prevent breast cancer progression. Quercetin, kaempferol, and rosmarinic acid were selected to explore their potential bioactivities. Each polyphenol was formulated into a microemulsion to improve its bioactivity and bioavailability. In vitro antioxidant and cytotoxicity activities of the selected polyphenols and their microemulsion forms were further investigated. The optimized microemulsion carrier with 1% oleic acid, 3% ethanol, 10% polysorbate 20, and 86% ultrapure water achieved more than 90% polyphenol encapsulation efficiency. The microemulsion was stable for more than 30 days when encapsulating polyphenol in the fluctuating temperature treatment. In vitro studies suggested that rosmarinic acid-loaded microemulsion had the best antioxidant activity compared with other polyphenol-loaded microemulsions (PL-MEs). Blank microemulsion and all PL-MEs significantly inhibited the proliferation of both hormone-dependent (T47D) and hormone-independent (MDA-MB-231) breast cancer cells. More studies are warranted to confirm the contribution of the microemulsion carrier components to the polyphenols’ improved antioxidant activity and high toxicity of PL-MEs on breast cancer cells. Full article
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13 pages, 1643 KiB  
Article
Quantitative 1H NMR Spectroscopy Method for Determination of Anthraquinone Derivatives in Extracts from Rubia tinctorum L. Roots and Rhizomes
by Vasilii Vasil’ev, Anzhelika Sheremeta, Vasilii Ivlev, Sergey Goriainov, Fadi Hajjar, Cesar Esparza, Evgeniy Platonov, Arkadiy Khromov, Alexandr Kolesnov, Victoria Romashchenko and Gennady Kalabin
Sci. Pharm. 2024, 92(2), 24; https://doi.org/10.3390/scipharm92020024 - 4 May 2024
Viewed by 1554
Abstract
The roots and rhizomes of Rubia tinctorum L. have been widely used both for industrial and medicinal purposes for centuries. The primary biologically active substances from Rubia tinctorum L. roots and rhizomes are anthraquinone derivatives such as ruberythric acid and lucidin-3-primeveroside. Their identification [...] Read more.
The roots and rhizomes of Rubia tinctorum L. have been widely used both for industrial and medicinal purposes for centuries. The primary biologically active substances from Rubia tinctorum L. roots and rhizomes are anthraquinone derivatives such as ruberythric acid and lucidin-3-primeveroside. Their identification and quantification are carried out by various analytical methods, requiring a complicated sample preparation as well as special reagents and reference samples. However, NMR spectroscopy has no limitations of this kind. In this work, we have developed and validated a new express and standard-free method for the qualitative and quantitative analysis of ruberythric acid and lucidin-3-primeveroside by 1H NMR spectroscopy in the extracts from the roots and rhizomes of Rubia tinctorum L. In this work, we have optimized the conditions of the sample preparation and registration of 1H NMR spectra, determined the optimal solvent and reference compound and confirmed the obtained results by HPLC-UV-MS. Full article
(This article belongs to the Topic Natural Products and Drug Discovery)
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16 pages, 336 KiB  
Review
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 1 | Viewed by 4758
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)
22 pages, 6185 KiB  
Article
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 1766
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  
Article
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 2037
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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8 pages, 1434 KiB  
Communication
Nanosized Particles of Synthetic Silicon Dioxide Delay the Regeneration of Gastric Ulcers Created by N-Methyl-N′-Nitro-N-Nitrosoguanidine and Induce Hyper-Trophic Gastritis-like Symptoms
by Ayaka Iwasaki, Yuichi Kawai and Akira Onodera
Sci. Pharm. 2024, 92(2), 20; https://doi.org/10.3390/scipharm92020020 - 11 Apr 2024
Viewed by 1562
Abstract
Synthetically produced silicon dioxide used as a food additive exhibits nanoparticle size and shape during the early stages of manufacturing. Even when processed into food products, these nanoparticles are detected. Although processing food ingredients into nanoparticles can improve absorption rates or enhance texture, [...] Read more.
Synthetically produced silicon dioxide used as a food additive exhibits nanoparticle size and shape during the early stages of manufacturing. Even when processed into food products, these nanoparticles are detected. Although processing food ingredients into nanoparticles can improve absorption rates or enhance texture, there are concerns about the specific biological effects of nanoparticles. In this study, three types of silica particles, including nanosized particles, were repetitively administered to the stomach using a gastric tube or exposed to a single injection into the submucosal layer of the stomach. Macroscopic and microscopic examinations did not reveal acute toxicity. However, when silica particles were administered to the stomach during the healing and regeneration process of gastric ulcers (induced by injecting the alkylating agent of N-Methyl-N′-Nitro-N-Nitrosoguanidine into the submucosal layer), silica particles with a diameter of 70 nm (SiNPs-70) delayed regeneration more strongly than microsized silica particles with diameters of 300 nm or 1000 nm (SiMPs-300, -1000). Furthermore, fibrosis for tissue regeneration spread throughout the entire mucosa of the stomach, resulting in hypertrophic gastritis-like symptoms. The frequency of this symptom was over 50% with SiNPs-70, 20% with SiMPs-300, and 0% with SiMPs-1000. Although the silica particles used in this study differ from actual samples found in food, the impact of particle size, particularly the effects unique to nanosize, was identified as toxicity in the stomach healing process. Full article
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15 pages, 3098 KiB  
Article
β-Sitosterol Mediates Gastrointestinal Smooth Muscle Relaxation Induced by Coccoloba uvifera via Muscarinic Acetylcholine Receptor Subtype 3
by Francisco J. Aguirre-Crespo, José L. Aragón-Gastélum, Eduardo J. Gutiérrez-Alcántara, Pedro Zamora-Crescencio, Diana L. Gómez-Galicia, Diego R. Alatriste-Kurzel, Guzman Alvarez and Emanuel Hernández-Núñez
Sci. Pharm. 2024, 92(2), 19; https://doi.org/10.3390/scipharm92020019 - 5 Apr 2024
Viewed by 1917
Abstract
Coccoloba uvifera is a Mayan medicinal plant, and these leaves are used as antidiarrheal and diuretic agents. In the present work, we develop in-vitro, ex-vivo, in-vivo, and in-silico strategies to evaluate several aqueous extracts of C. uvifera leaves. In vitro tests showed that [...] Read more.
Coccoloba uvifera is a Mayan medicinal plant, and these leaves are used as antidiarrheal and diuretic agents. In the present work, we develop in-vitro, ex-vivo, in-vivo, and in-silico strategies to evaluate several aqueous extracts of C. uvifera leaves. In vitro tests showed that decoction extract (CuDe) presented the best yield and chlorophyll, phenol, and flavonoid content; however, CuDe showed low antioxidant activity (DPPH model). All aqueous extracts exert spasmolytic and vasorelaxant activity in a concentration-dependent manner (ex vivo), and in vivo tests showed that CuDe exerts the best antiperistaltic and diuretic effects. The in-silico analysis suggests that C. uvifera triterpenes act as a ligand of GPCR, and β-sitosterol could act as an antagonist of muscarinic acetylcholine receptor subtype 3 (m3AChR). In the context of aqueous extracts of C. uvifera, β-sitosterol and their heterosides were identified by FTIR and 1H-NMR spectroscopy. The concerted binding of β-sitosterol and other triterpenes within the m3AChR binding site may be relevant for the induction of relaxant effects at the gastrointestinal smooth muscle level. In this context, C. uvifera is a high-value plant species that requires analytical and pharmacological studies to confirm traditional medicinal use. Full article
(This article belongs to the Topic Natural Products and Drug Discovery)
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20 pages, 6519 KiB  
Article
Synthesis, Biological Evaluation, Molecular Docking and ADME Studies of Novel Pyrrole-Based Schiff Bases as Dual Acting MAO/AChE Inhibitors
by Emilio Mateev, Magdalena Kondeva-Burdina, Maya Georgieva, Alexandrina Mateeva, Iva Valkova, Virginia Tzankova and Alexander Zlatkov
Sci. Pharm. 2024, 92(2), 18; https://doi.org/10.3390/scipharm92020018 - 29 Mar 2024
Viewed by 1840
Abstract
Considering the complex pathogenesis of Alzheimer’s disease (AD), the multitarget ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target approach. Thus, a series of 13 novel (5e-q) pyrrole-based Schiff [...] Read more.
Considering the complex pathogenesis of Alzheimer’s disease (AD), the multitarget ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target approach. Thus, a series of 13 novel (5e-q) pyrrole-based Schiff bases were synthesized by conventional and microwave-assisted condensations, and the compounds were evaluated for MAO-A, MAO-B and AChE inhibitory activities. The chemical structures of the newly formed molecules were elucidated by a combination of spectral methods. The obtained results confirmed the theoretical data. The majority of the title Schiff bases demonstrated good potential towards AChE at 10 μM concentrations, with the most promising compound 5m (58%) exerting a comparative effect to that of the applied standard—Donepezil. 5j and 5o selectively inhibited MAO-B by 26% and 21% (at 1 μM concentration), respectively. The compound condensed with 5-nitro-2-furaldehyde (5j) achieved the best dual MAO-B and AChE inhibitory capacities. In addition to the in vitro analysis, docking simulations targeting the active sites of AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z) were employed to explore the possible interactions of the most prominent dual inhibitor (5j) with the enzymes. Furthermore, in silico ADME and PAMPA-blood–brain barrier (BBB) studies were conducted. Full article
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13 pages, 2456 KiB  
Article
Semaglutide as a Possible Calmodulin Binder: Ligand-Based Computational Analyses and Relevance to Its Associated Reward and Appetitive Behaviour Actions
by Giuseppe Floresta, Davide Arillotta, Valeria Catalani, Gabriele Duccio Papanti Pelletier, John Martin Corkery, Amira Guirguis and Fabrizio Schifano
Sci. Pharm. 2024, 92(2), 17; https://doi.org/10.3390/scipharm92020017 - 22 Mar 2024
Cited by 1 | Viewed by 2497
Abstract
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has gained considerable attention as a therapeutic agent for type 2 diabetes mellitus and obesity. Despite its clinical success, the precise mechanisms underlying its pharmacological effects remain incompletely understood. In this study, we employed ligand-based drug [...] Read more.
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has gained considerable attention as a therapeutic agent for type 2 diabetes mellitus and obesity. Despite its clinical success, the precise mechanisms underlying its pharmacological effects remain incompletely understood. In this study, we employed ligand-based drug design strategies to investigate potential off-target interactions of semaglutide. Through a comprehensive in silico screening of semaglutide’s structural properties against a diverse panel of proteins, we have identified calmodulin (CaM) as a putative novel target of semaglutide. Molecular docking simulations revealed a strong interaction between semaglutide and CaM, characterized by favourable binding energies and a stable binding pose. Further molecular dynamics simulations confirmed the stability of the semaglutide–CaM complex, emphasizing the potential for a physiologically relevant interaction. In conclusion, our ligand-based drug design approach has uncovered calmodulin as a potential novel target of semaglutide. This discovery sheds light on the complex pharmacological profile of semaglutide and offers a promising direction for further research into the development of innovative therapeutic strategies for metabolic disorders. The CaM, and especially so the CaMKII, system is central in the experience of both drug- and natural-related reward. It is here hypothesized that, due to semaglutide binding, the reward pathway-based calmodulin system may be activated, and/or differently regulated. This may result in the positive semaglutide action on appetitive behaviour. Further studies are required to confirm these findings. Full article
(This article belongs to the Topic Bioinformatics in Drug Design and Discovery—2nd Edition)
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