Saudi Pharmaceutical Journal最新文献

Carbohydrate analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we explored the various therapeutic potential of methyl α-D-mannopyranoside (MαDM) analogs, including their ability to synthesize and assess their antibacterial, antifungal, and anticancer properties; additionally, molecular docking, molecular dynamics simulation, and ADMET analysis were performed. The structure of the synthesized MαDM analogs was ascertained by spectroscopic techniques and physicochemical and elemental analysis. In vitro antimicrobial activity was assessed and revealed significant inhibitory effects, particularly against gram-negative bacteria along with the prediction of activity spectra for substances (PASS). Concurrently, MαDM analogs showed good results against antifungal pathogens and exhibited promising anticancer effects in vitro, demonstrating dose-dependent cytotoxicity against Ehrlich ascites carcinoma (EAC) cancer cells while sparing normal cells from compound 5, with an IC₅₀ of 4511.65 µg/mL according to the MTT colorimetric assay. A structure–activity relationship (SAR) study revealed that hexose combined with the acyl chains of decanoyl (C-10) and benzenesulfonyl (C₆H₅SO₂-) had synergistic effects on the bacteria and fungi that were examined. Molecular docking was performed against the Escherichia coli (6KZV) and Candida albicans (1EAG) proteins to acquire insights into the molecular interactions underlying the observed biological activities. The docking results were further supported by 100 ns molecular dynamics simulations, which provided a dynamic view of the stability and flexibility of complexes involving MαDM and its targets. In addition, ADMET analysis was used to evaluate the toxicological and pharmacokinetic profiles. Owing to their promising drug-like properties, these MαDM analogs exhibit potential as prospective therapeutic candidates for future development.

Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol compounds on surgical-induced peritoneal adhesion, and their strategies that disrupted the PA formation pathways to suppress their incidence. First, liquid chromatography-mass spectrometry (LC-MS) was established to separate and identify several chemical groups of ginger rhizome extract. In the next steps, male Wistar albino rats were randomly selected and divided into various groups, namely sham, control, ginger extract (0.6, 1.8, 5 %w/v), and gingerol (0.05, 0.1, 0.3, and 1 %w/v). Finally, we investigated the macroscopic parameters such as wound healing, body weight as well as spleen height and weight. In addition, visual peritoneal adhesion assessment was performed via Nair et al and Adhesion Scoring Scheme. Moreover, the microscopic parameters and biological assessment was performed via and immunoassays. The present findings revealed significant improvement in wound healing and reduction of the adhesion range, as Nair et al. and Adhesion Scoring Scheme scoring, in both the ginger and gingerol groups compared to the PA group (P < 0.05). Whereas, gingerol (0.3 % w/v) was able to increase the body weight in rats (P < 0.0001) at end stage of experiment. Also, inflammation, angiogenesis, and fibrosis were significantly decreased due to the downregulation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), respectively, in the ginger and gingerol groups compared to the PA group (P < 0.05). In contrast, the levels of IL-10 were increased in the ginger and gingerol groups compared to the control group (P < 0.01). Our results proved that ginger rhizome and gingerol, as novel therapeutic compounds, could be used to prevent PA for their beneficial anti-inflammatory as well as anti-fibrosis properties in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger and gingerol.

Fixed-dose combination (FDC) products represent a novel, safe, and cost-effective formulation. Combined use of anticoagulant and antiplatelet medications is common among comorbid cardiovascular patients. This study aimed to formulate FDC tablets for Apixaban and Clopidogrel, as prophylaxis and treatment of thrombo-embolic events. FDC tablets were developed by combining small tablets of Immediate-Release Clopidogrel 75 mg and Extend-Release Apixaban 5 mg through direct compression and wet granulation. Particularly, Apixaban tablets were developed using design expert software, and various types and concentrations of polymers were entered. For Clopidogrel tablets, various diluents were used to develop the formulation. Then, the dissolution profile for each formula was studied. Finally, the optimized formulations were encapsulated within hard gelatin capsules. Apixaban formulation followed zero-order with super case Ⅱ transport mechanism as the dominant mechanism of drug release. The Apixaban drug release rate was affected by the type and concentration of the polymers in the formulation (P < 0.05). As the HPMC concentration was increased, Apixaban release was retarded. For, Clopidogrel, the formulated tablets with spray-dried lactose filler and sodium stearyl fumarate lubricant were found to be stable with good properties. In conclusion, the optimum formulation yielded Clopidogrel and extended-release Apixaban for 24 h with the desired in vitro drug dissolution.

Introduction

Saudi Arabia has begun reforming its government-run health care system to increase efficiency and reduce costs. One effort is the adoption of an electronic prescribing system (Wasfaty) and outsourcing pharmaceutical services from government-run clinics to community pharmacies (CP). This study aims to compare satisfaction with pharmaceutical services offered in the two systems.

Materials and methods

This cross-sectional observational study used existing survey data collected from patients (≥15 years of age) visiting government primary health care centers from January 2022 to June 2022. Satisfaction with three pharmaceutical services (availability of medications, pharmacist’s explanation of the prescription, and waiting time to get medications) were the main outcomes.

Results

The study comprised 91,317 participants, 74.06 % of them were CP/Wasfaty users. CP/Wasfaty patients had lower odds of satisfaction with the three pharmaceutical services: availability of medications (OR = 0.49, 95 % CI = 0.47–0.51), pharmacists’ explanation of prescription (OR = 0.55, 95 % CI = 0.53–0.58), and waiting time to get medications (OR = 0.81, 95 % CI = 0.75–0.88). Additional findings showed variations in satisfaction levels based on demographic factors and clinic types.

Conclusions

The significant differences observed in satisfaction levels based on demographic characteristics and type of clinics visited emphasize the importance of tailoring pharmaceutical services to meet the specific needs and expectations of different patient populations.

This review discusses the potential of liposomes as drug delivery systems for antimalarial therapies. Malaria continues to be a significant cause of mortality and morbidity, particularly among children and pregnant women. Drug resistance due to patient non-compliance and troublesome side effects remains a significant challenge in antimalarial treatment. Liposomes, as targeted and efficient drug carriers, have garnered attention owing to their ability to address these issues. Liposomes encapsulate hydrophilic and/or hydrophobic drugs, thus providing comprehensive and suitable therapeutic drug delivery.

Moreover, the potential of passive and active drug delivery enables drug concentration in specific target tissues while reducing adverse effects. However, successful liposome formulation is influenced by various factors, including drug physicochemical characteristics and physiological barriers encountered during drug delivery. To overcome these challenges, researchers have explored modifications in liposome nanocarriers to achieve efficient drug loading, controlled release, and system stability. Computational approaches have also been adopted to predict liposome system stability, membrane integrity, and drug-liposome interactions, improving formulation development efficiency. By leveraging computational methods, optimizing liposomal drug delivery systems holds promise for enhancing treatment efficacy and minimizing side effects in malaria therapy. This review consolidates the current understanding and highlights the potential of liposome strategies against malaria.

Background and objective

Complementary and alternative medicine (CAM) is a common practice among patients, who experience functional gastrointestinal disorders (FGID). Among the Saudi population, less is known about CAM use for FGID. Therefore, this study aimed to determine the prevalence of CAM utilization for FGID amongst the Saudi population and determine the types of CAM used for treatment.

Method

A cross-sectional study was carried out in Riyadh, Saudi Arabia during February 2023 through social media platforms using questionnaires adopted from the literature. There were three sections in the questionnaire including demographic information, questions to determine the prevalence of CAM use for FGID, the types of FGID, and the types of CAM utilization, and questions on the sources of information about CAM. Multivariable logistic regression was applied to find factors associated with CAM use. All statistical analyses were performed using SPSS version 26.

Results

A total of 828 people participated in this study. The overall prevalence of CAM use for FGID problems was 87.2 %. There were no significant differences in CAM use for FGID problems between men (87.5 %) and women (86.3 %) (P = 0.727). The most commonly used types of CAM for FGID were ginger (73.4 %), chamomile (66.6 %), mint (61.6 %), turmeric (59.0 %), anise (55.5 %), fennel (43.1 %), and Activia yogurt©️ (42.7 %). The most common FGID disorders for utilizing CAM were IBS (29.9 %), followed by constipation (29.8 %), dyspepsia (22.7 %), and bloating (17.0 %). In the multivariable regression, age, gender and employment status did not have an impact on the odds of using CAM. The subjects who had high school, university, and postgraduate education had significant odds ratios of CAM use (OR = 2.73; 95 % CI: 1.22–6.13), (OR = 4.18; 95 % CI: 2.03–8.58), and (OR = 20.85; 95 % CI: 5.51–78.80), respectively, compared to subjects who did not complete high school. Participants who had private insurance had a significant odds ratio (OR = 0.27; 95 % CI: 0.14–0.55) compared to governmental insurance.

Conclusion

The use of CAM among the Saudi population is alarmingly high; however, the lack of standardized medical recommendations and treatment options may be the cause. Although there were no significant gender differences, participants with higher educational levels and private insurance coverage were more likely to use CAM for FGID. Patients suffering from FGID and limited access to medical advice and treatment options are vulnerable to being exposed to dubious and incredible information sources. Expanding access to preventative medical services, funding governmental medical websites to provide credible information, educating healthcare professionals about FGID, and conducting more research in safe and effective treatments for FGID is recommended.

Background and Objective

Glucose-Potassium Ratio (GPR) has emerged as a biomarker in several pathophysiological conditions. However, the association between GPR and long-term outcomes in stroke patients has not been investigated. Our study evaluated the applicability of baseline GPR as a predictive prognostic tool for clinical outcomes in ischemic stroke patients.

Methods

The multicenter retrospective cohort study included acute-subacute adult ischemic stroke patients who had their baseline serum GPR levels measured. Eligible patients were categorized into two sub-cohorts based on the baseline GPR levels (<1.67 vs. ≥ 1.67). The primary outcome was the incidence of 30-day hemorrhagic transformation, while stroke recurrence, and all-cause mortality within twelve months, were considered secondary.

Results

Among 4083 patients screened, 1047 were included in the current study. In comparison with GPR < 1.67 group, patients with ≥ 1.67 GPR had a significantly higher ratio of all-cause mortality within twelve months (aHR 2.07 [95 % CI 1.21–3.75] p = 0.01), and higher ratio of 30-day hemorrhagic transformation but failed to reach the statistical significance (aHR 1.60 [95 % CI 0.95–2.79], p = 0.08).

Conclusion

Overall, baseline GPR serum is an independent predictor of all-cause mortality within twelve months in patients with acute and subacute ischemic stroke. Further clinical studies are necessary to validate these findings.

Silymarin (SLR) is a poorly water-soluble bioactive compound with a wide range of therapeutic activities. Nanosized silymarin vesicles (F1–F6) were prepared by the solvent evaporation rehydration method. The silymarin vesicles were evaluated for vesicle size, surface charge, entrapment efficiency, and drug release studies. The optimized SLR lipid vesicle (F3) was further modified with the addition of the cationic polymer chitosan. After that, the modified vesicle (F3C1) was assessed for permeation flux, antimicrobial activity, cell viability, and molecular docking studies. The silymarin vesicles showed nanometric size (<250 nm), low polydispersibility index (<0.05), negative surface charge, and high SLR entrapment (85–95 %). The drug release study result demonstrated a maximum drug release of 91.2 ± 2.8 %. After adding chitosan to the surface, there was a significant change in the size, polydispersibility index, surface charge (positive), and encapsulation efficiency. The drug release was found to be prolonged, and the permeation flux was also increased in comparison to free SLR. A comparative antimicrobial result was observed in comparison to the free SLR and standard drug. The cell viability assay also demonstrated a low IC₅₀ value for F3C1 against the cell line.

The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. KSG markedly increased the survival rate and alleviated lung pathological lesions induced by lipopolysaccharide (LPS). Furthermore, KSG attenuated differential and total cell counts in BALF (bronchoalveolar lavage fluid) and MPO (myeloperoxidase) activity. KSG counteracted the NF-κB (nuclear factor-κB) activation and significantly ameliorated the downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, KSG suppressed the over-expression of NLRP3 (NOD-like receptor protein 3), caspase-1, and pro-inflammatory cytokine interleukin IL-1β (interleukine-1β) and prohibited the elevation of the pyroptotic parameter GSDMD-N (N-terminal domain of gasdermin D) induced by LPS challenge. In addition, KSG significantly enhanced Nrf2 (nuclear-factor erythroid-2-related factor) and HO-1 (heme-oxygenase-1) expression. Meanwhile, KSG mitigated lipid peroxidative markers (malondialdehyde, protein carbonyl and 4-hydroxynonenal) and boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) in lung tissue. In silico analyses revealed that KSG disrupts Keap1-Nrf2 protein–protein interactions by binding to the KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior binding affinity of KSG to KEAP1 compared to the reference inhibitor, with docking scores of −9.576 and −6.633 Kcal/mol, respectively. Additionally, the MM-GBSA binding free energy of KSG (−67.25 Kcal/mol) surpassed that of the reference inhibitor (−56.36 Kcal/mol). Furthermore, MD simulation analysis revealed that the KSG-KEAP1 complex exhibits substantial and stable binding interactions with various amino acids over a duration of 100 ns. These findings showed the protective anti-inflammatory and anti-oxidative modulatory efficiencies of KSG that effectively counteracted LPS-induced ALI and encouraged future research and clinical applications of KSG as a protective strategy for ALI.