Sci. Pharm., Volume 92, Issue 1 (March 2024) – 16 articles

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

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

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

Benign prostatic hyperplasia (BPH) is a common disease in aging men. Panicum dichotomiflorum (PD) is an annual grass species of Poaceae that is distributed worldwide. The present study examined whether PD has a protective effect against BPH. BPH was generated in rats by daily subcutaneous administration of testosterone for four weeks. During this period, the rats were also given daily oral gavages of an extract of PD (150 mg/kg). After the final treatment, all animals were euthanized and their prostates were collected and weighed. In BPH model rats, the prostate weight and levels of dihydrotestosterone (DHT) and 5α-reductase expression were inhibited following treatment with PD extract. Testosterone-induced increases in prostate gland epithelial thickness and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) were markedly suppressed in PD-treated rats, whereas cleaved caspase-3 levels were increased. PD administration also decreased the expression of transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF), the phosphorylation of Akt, and inflammatory cytokines levels. Taken together, these results show that PD extract protects against testosterone-induced BPH progression by alleviating prostate cell growth and reducing levels of growth factors and inflammatory cytokines, indicating that PD extract may have potential in protecting against BPH. Full article

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

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

(1) Background: The study aimed to compare the impact of various natural polymers–sodium alginate, acacia gum, carrageenan, guar gum, xanthan gum, and tragacanth on the formulation and the physical properties of mucoadhesive vaginal tablets containing metronidazole (167 mg/g). (2) Methods: The quality of the tablets prepared by direct compression was evaluated by pharmacopoeia tests (uniformity of mass, resistance to crushing, friability). Mucoadhesion of the tablets was characterized by swelling capacity and mucoadhesive strength, i.e., the force required to detach the tablet from the rabbit mucosa. In vitro drug release was performed by a modified dissolution method in paddle apparatus containing the simulated vaginal fluid (pH 4.5). Scanning electron microscopy observed morphological changes on the swollen tablets’ surface. (3) Results: Pharmacopoeia tests have shown that all prepared tablets met the requirements on quality. The highest mucoadhesive strength was noted in tablets containing guar and xanthan gum. The highest swelling capacity was possessed by tablets containing carrageenan. (4) Conclusions: Summarizing all tests’ results, sodium alginate can be considered the most suitable natural polymer in tablet formulation. The combination of polymers providing higher mucoadhesiveness and at the same time a prolonged release, e.g., xanthan or guar, together with sodium alginate, could also be of interest. Full article

Zoapatle, a native plant utilized for centuries in traditional Mexican medicine, is abundantly found in Mesoamerica and northern South America. Pleiotropic effects of this genus have been recognized, primarily inducing alterations in smooth muscle contractility in animal models. The aim of this study was to evaluate the effect of Zoapatle on the hypertrophy index and the gene expression of TNF-α, IL-1β, NF-κB, STAT5, and the PRLR in the brain, left ventricle, and renal cortex of rats with isoproterenol-induced cardiac hypertrophy. Three groups were studied, the control group (n = 4), hypertrophy group (n = 4) and hypertrophy group treated with Zoapatle (n = 4). A ventricular hypertrophy model was developed with 150 mg/kg/day of isoproterenol intraperitoneally administered over two days with a 24 h interval between applications. Zoapatle was administered for 28 consecutive days (25 mg/kg). Gene expression was determined with RT-qPCR. Subsequently, a principal component analysis (PCA) was performed using the RNA expression variables. A notably reduced left ventricle mass index was observed in the Zoapatle group. Additionally, Zoapatle administration in cardiac hypertrophy demonstrated a significant decrease in the gene expression of TNF-α, IL-1B, STAT 5, and the PRLR. TNF-α and the transcription factor STAT5 exhibited a similar trend in both the left ventricle and renal cortex, suggesting a correlation with the inflammatory state in these tissues due to ventricular hypertrophy. The findings suggest that Zoapatle reverses the hypertrophy index in a hypertrophy model, concurrently reducing several proinflammatory mediators associated with the hypertrophy index. Full article

The design, development, and release kinetics of omeprazole (OME) from solid dosage forms have been investigated. These formulations were examined for their resilience in pH = 4.5 buffer solutions and their rate of disintegration in a small-intestine-like environment (pH = 6.8). The results were compared with those of the well-known brand product Losec^®, where its use is accompanied by numerous benefits but drawbacks as well. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) tests were conducted in order to examine the release kinetics of the various dosage forms and provide explanations based on the interactions between the excipients and the active substance. Full article

Easy access to over-the-counter (OTC) drugs makes it possible to procure active substances that normally used in therapeutic doses do not raise health problems. The use of high doses of OTC drugs containing codeine, loperamide, pseudoephedrine, diphenhydramine or dimenhydrinate, as well as the use of benzidamine systemically raises concerns regarding the increase in units sold. These drugs are used for recreational or euphorizing purposes, including by young women of childbearing age, psychoactive substance users representing a risk group in terms of the possibility of an unplanned pregnancy. Abusive consumption of OTC products during pregnancy is harmful, with consequences for both fetal and late development that can occur in the infant. This literature review presents the risks (teratogenicity, fetal toxicity, neonatal abstinence syndrome, etc.) associated with the use of potentially psychoactive OTC drugs to emphasize the importance of re-evaluating OTC classification and dispensing. Full article

Calophyllum inophyllum L. has been used for many generations by Pacific Islanders because of its numerous health and aesthetic advantages. The leaves, stems, roots, fruits, flowers, and seeds of this plant contain significant phytochemicals, including flavonoids, coumarins, fatty acids, and xanthones, which have been shown to have wound healing, analgesic, anti-inflammatory, antiaging, anti-arthritic, anti-cancer, anti-proliferative, anti-diabetic, anti-microbial, and anti-HIV effects. The chemical profiles and bioactive potential may vary due to different extraction techniques, plant parts, and geographical origins. Extraction is the essential first step in the analysis of bioactive compounds that leads to further separation, identification, and characterization. Conventional methods like maceration, Soxhlet, and percolation are often used to extract bioactive compounds from C. inophyllum. However, little study has been carried out on non-conventional methods such as pressured liquid extraction, supercritical fluid extraction (SFE), and ultrasound-assisted extraction. The SFE method can be used to extract bioactive compounds from C. inophyllum to retain their pharmacological properties for application in pharmaceutical and cosmetic products. Full article

Taxifolin is a natural polyphenol belonging to the class of flavonoids. The structure of this compound is characterized by the presence of two chiral centers. The spheroidal form of taxifolin (TAXs) has emerged as a promising modification due to enhanced solubility, higher safety profile, and long-term release from solid dosage forms. The study’s objective was to assess the diastereomeric content in TAXs and industrially produced samples of taxifolin. Considering the difference in the physico-chemical properties of diastereomers and based on the literature data, we developed a qualitative HPLC method. The chromatograms were recorded using a diode array detector at 290 nm and a mass spectrometer operated in negative ionization mode. Our data suggest that a biphenyl column and gradient elution using 0.1% formic acid in water and 0.2% formic acid in methanol, with the organic phase gradient from 7% to 21% and a flow rate of 0.65 mL/min for 15 min at 60 °C, provides the best conditions for the separation of taxifolin diastereomers. This method was validated for quantitative analysis. We discovered that the cis-isomer was present in all the analyzed samples, with its quantity ranging from 0.8% to 9.5%. TAXs can be considered a sample enriched with diastereomers. Full article

This study introduces a novel approach for enhancing the transdermal permeability of ibuprofen through the skin by utilising a rotating magnetic field (RMF). The core objective is to systematically evaluate the influence of a 50 Hz RMF on ibuprofen’s skin permeability across various formulation types, each employing distinct physical forms and excipients. The experimental setup involved Franz cells with skin as the membrane, exposed to a 50 Hz RMF in conjunction with specific formulations. Subsequent comprehensive analysis revealed a notable increase in the transdermal transport of ibuprofen, irrespective of the formulation employed. Notably, the differences in the initial 30 min of permeation were particularly pronounced. Crucially, this investigation establishes that the application of a 50 Hz RMF resulted in a remarkable over-sevenfold increase in ibuprofen permeability compared to the control group without RMF exposure. It is noteworthy that in all semi-solid pharmaceutical formulations tested, RMF effectively reduced the delay time to zero, underscoring the efficiency of RMF in overcoming barriers to transdermal drug delivery. This research positions the application of RMF as a highly promising and innovative technology, significantly enhancing the transdermal penetration of anti-inflammatory and analgesic drugs through the skin. The demonstrated effectiveness of RMF across diverse formulations suggests its potential in transdermal drug delivery, offering a novel and efficient strategy for improving therapeutic outcomes in the administration of ibuprofen and potentially other pharmaceutical agents. Full article

Atopic dermatitis (AD) is increasingly prevalent globally. However, the frequent and prolonged use of corticosteroids, which are commonly employed for AD treatment, carries potential side effects. Korean mistletoe (Viscum album L. var. coloratum), a perennial parasitic plant, has demonstrated various biological effects. In this study, we conducted in vivo investigations to determine whether Korean mistletoe possesses anti-inflammatory effects that play pivotal roles in regulating the pathological mechanisms of AD. BALB/c mice with AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) were utilized to explore the therapeutic effects of 1% and 2% Korean mistletoe extract (KME) ointments. The KME ointment was topically applied to the dorsal surface of the BALB/c mice, and they were categorized into four distinct groups: normal, DNCB-induced, DNCB-induced with 1% KME ointment, and DNCB-induced with 2% KME ointment. Each assessment parameter employed to evaluate the curative impact of the KME ointment displayed improvement with the application of the 1% KME ointment. While the effects observed were less pronounced than those of the 1% KME ointment, the overall therapeutic outcomes were also evident with the utilization of the 2% KME ointment. The results suggest the potential of Korean mistletoe as a viable therapeutic agent for AD. Further investigations are warranted to elucidate the underlying mechanisms of action. Full article

The aim of this study was to establish the relationship between different polymorphisms in drug transporter and metabolizer genes and resistance to imatinib in chronic myeloid leukemia (CML). For this purpose, an exhaustive search was carried out in the Scopus, Web of Science, and PubMed databases using different combinations of keywords with different inclusion and exclusion criteria. The meta-analysis included nine studies that met the established criteria. The results of the study showed that the polymorphic variants AG and GG of CYP3A5*3 are associated with response to treatment, presenting a significantly lower risk with resistance to imatinib. Likewise, the variants T1236C and G2677T/A of the ABCB1 gene show a significant association with treatment efficacy. In addition, the genetic polymorphism 1236T, homozygous CC of the MDR1 gene, significantly influences the increased risk of cytogenetic relapse and the polymorphic variant 361G>A GA of the SLCO1A2 gene significantly affects the complete molecular response. Full article

The need for new antimicrobial agents (AntAg) is driven by the persistent antibiotic resistance in microorganisms, as well as the increasing frequency of pandemics. Due to the deficiency of AntAg, research aimed at developing speedy approaches to find new drug candidates is relevant. This study aims to conduct an in silico study of the biological activity spectrum as well as the molecular binding mechanisms of four structurally different forms of levofloxacin (Lvf) with bacterial topoisomerases targets of type IIA (DNA gyrase and topoisomerase IV) to enable the development of drugs with an improved characterization of the safety profile. To achieve this goal, a number of software products were used, such as ChemicPen v. 2.6, PyMol 2.5, Avogadro 1.2.0, PASS, AutoDockTools 1.5.7 with the new generation software Autodock Vina. These software products are the first to be made available for visualization of clusters with determination of ligand-receptor pair binding affinity, as well as clustering coordinates and proposed mechanisms of action. One of the real structures of Lvf, a decarboxylated derivative, was obtained with tribochemical (TrbCh) exposure. The action spectrum of molecular ligands is described based on a Bayesian probability activity prediction model (PASS software Version 2.0). Predicted and real (PMS and RMS) molecular structures of Lvf, with decreasing levels of structural complexity, were translated into descriptors via Wiener (W), Balaban (Vs), Detour (Ip), and Electropy € indices. The 2D «structure-activity» diagrams were used to differentiate closely related structures of levofloxacin. PMS and RMS were visualized as 3D models of the ligand-receptor complexes. The contact regions of RMS and PMS with key amino acid residues—SER-79, DT-15, DG-1, DA-1—were demonstrated. The intra- and inter-molecular binding sites, data on free energy (affinity values, kcal/mol), the binding constant K_b (M⁻¹), and the number of clusters are presented. The research results obtained from the presented in silico approach to explore the spectrum of action find quantitative “structure-activity” correlations, and predict molecular mechanisms may be of applied interest for directed drug discovery. Full article