Future Journal of Pharmaceutical Sciences最新文献

Background

Acinetobacter baumannii, a nosocomial pathogen, has emerged as a major clinical threat due to its ability to resist a broad range of antibiotics, contributing to the increased morbidity and mortality in hospital settings. This characteristic of Acinetobacter baumannii as a multiple-drug resistant (MDR) organism poses a critical global health challenge, necessitating an urgent need for alternative therapeutic strategies, such as vaccine development, as a preventive measure. In this study, we employ the method of reverse vaccinology and immunoinformatic tools to design a novel rRNA-based vaccine targeting the 16S and 23S rRNA of Acinetobacter baumannii.

Results

16S and 23S rRNA sequences of Acinetobacter baumannii were retrieved from the National Center for Biotechnology Information database (NCBI). The B and T cells’ epitopes were predicted from these retrieved sequences using bioinformatics tools. The epitopes generated were further analyzed for antigenicity, toxicity, and allergenicity. The epitopes that passed these screenings, including key structural elements, were used in the design of the vaccine. The vaccine constructs were further assessed for their physicochemical properties and dynamics. Structural modeling and molecular docking studies confirmed effective binding to Toll-like receptor 4 (TLR-4), while immune simulations demonstrated the potential to elicit robust and durable immune responses.

Conclusions

This study demonstrates the potential of reverse vaccinology and immunoinformatics approaches in designing a novel rRNA-based vaccine targeting the 16S and 23S rRNA of Acinetobacter baumannii. By identifying highly antigenic, non-toxic, and non-allergenic epitopes and incorporating them into a structurally optimized rRNA-based vaccine construct, we present a promising candidate capable of eliciting strong immune responses. However, limitations such as the unavailability of datasets, especially on the 5S rRNA region in the databases, are a roadblock that needs to be addressed.

Background

Patients with chronic diseases often have difficulties in managing multiple medications, resulting in poor adherence and, subsequently, adverse health consequences. Extensive research has demonstrated the beneficial effects of medication management devices, such as pill box organizers (PBOs) on enhancing medications adherence and improving patients’ health outcomes. However, research on PBOs in Egypt is limited. This study seeks to assess the awareness, user satisfaction of PBOs and their influence on medication adherence among Egyptian people with chronic illnesses.

Methods

Fifty -six Egyptian adults participated in a prospective observational study. Participants were recruited from two locations: a university employee and community individuals. Participants were asked to use a pillbox organizer for three months. Demographic data were gathered at baseline. During a bi-weekly interviews, we calculated missing doses for the past two weeks. At the end of the study period, a questionnaire containing yes/no questions to assess patients' awareness and PBO feasibility was conducted. The acceptability, usability, medication management support, and satisfaction of patients with the device were evaluated using a Likert scale.

Results

Sixty-one percent of the participants were aged 50 years or older. Almost 66% individuals possessed no prior awareness of pillbox organizers (95% CI: 0.54, 0.78, p = 0.0162). Nearly 90% deemed PBO beneficial for drug adherence (95% CI: 0.95, 1.02, p = 0). Most of the participants (80%) believed the PBO user-friendly, while 89% indicated that the device assisted in reminding them to adhere to their prescription regimen. The mean satisfaction score was 4.02 (± 0.25) on a 5-point Likert scale. Ninety-one percent of interviewees indicated that they would acquire a PBO if required.

Conclusion

The study participants viewed the PBO as an acceptable and useful tool for managing multiple medications, despite their limited awareness of them. The higher satisfaction and perceived usefulness indicate the feasibility for using PBOs in the Egyptian healthcare environments as well as its impact in enhancing drug adherence. Future research could focus on evaluating long-term adherence and health outcomes.

Background

An oral selective phosphoinositide 3-kinase (PI3K) delta inhibitor, leniolisib, is currently being developed by Pharming Group NV. The drug has been in-licensed by Novartis to treat immunodeficiency diseases. This work aimed to create and verify a rapid and simple high-performance liquid chromatography technique for quantifying leniolisib in rat plasma. Sorafenib was utilized as the internal standard.

Results

A bioanalytical method was established for analyzing rat plasma using an Inertsil ODS-4 C₁₈ column with dimensions of 150 mm length, 4.6 mm internal diameter, 3.0 µm particle size and 10 nm pore size. The mobile phase was a mixture of acetonitrile and phosphate buffer with a pH of 7.4 in a 40:60 proportion. The flow rate was set at 1 ml/min, and the analyte was detected using PDA detection at a wavelength of 294 nm. A linear calibration curve consisting of seven points was produced within the concentration range of leniolisib in plasma, ranging from 150 to 6000 ng/ml. The accuracy ranged from 89.82 to 91.69%, and %CV was less than 6%. Further investigation of the pharmacokinetics of leniolisib in the oral solution at 10 mg/kg was carried out using the method that had been devised.

Conclusion

The proposed methodology is appropriate for the routine analysis of leniolisib in plasma samples, which is crucial for facilitating research on the drug's bioavailability and bioequivalence.

Background

Recently, the need for artificial intelligence (AI) and machine learning (ML) methods in drug development and research is gaining high concern and more grounds. Moreover, providing pharmaceutical and related schools with non-commercial, free-to-use programming languages, software and tools is becoming an unavoidable need. The R programming language can be easily used, through the correct and simplified codes and packages, in conducting unsupervised ML methods, such as principal component analysis (PCA) and hierarchical clustering analysis (HCA), after calculating relevant descriptors of drugs and molecules.

Objective

The objective of this study was to assess the enhancement of non-computer sciences-based students’ perception of the use of machine learning methods such as PCA and HCA using R-programming in drug formulation.

Results

Undergraduate students were taught to use R program to derive PCA distinguishable plots such as score, loading and scree, in addition to HCA dendrograms, in the context of developing new pharmaceutical formulations. Surveys conducted pre- and post-teaching the course proved that implementation of such ML methods can help in better understanding and exploring the data, in order to derive meaningful conclusions, and make informed decisions that help develop pharmaceutical formulations of premium quality, with minimal resources consumption.

Conclusion

We hereby report the easy use of R-programming in applications and activities that introduce undergraduate Pharmaceutical Engineering and Biotechnology students to ML methods. Student surveys showed better student satisfaction and understanding of AI applications in solving pharmaceutical problems. We claim that these students and early_career researchers, who are non-specialists in computer science, can utilize R-programming to perform important pharmaceutical applications through the step-by-step guide and codes provided in this article.

Graphical Abstract

Background

Skin integrity is crucial for human body normal physiological homeostasis. Skin wound management is critical to prevent progressive infection, scarring, and many other problems that could develop if wounds are not optimally treated. In this work, hyaluronic acid-coated silver nanoparticles loaded with vancomycin were evaluated as a potent comprehensive system to cure and inhibit infections of skin wounds.

Results

In vitro testing of the prepared silver nanoparticles was carried out, assaying its particle size, polydispersity index, zeta potential, and UV absorbance. Silver nanoparticles were optimized by applying two-factor three-level full factorial design utilizing Design-Expert® software. The optimum system showed particle size 399.71 nm ± 8.4, − 60.31 mV ± 4.6 for zeta potential, and 3.74 silver UV absorbance. In vivo study on surgically induced wounds in dogs manifested that the optimum drug-loaded system significantly boosted the wound healing process compared to plain system, drug solution, or control group providing rapid and complete skin regeneration. This was evidenced by clinical observations which showed significantly higher percent wound contraction and complete epithelization. Also, histopathological examinations revealed organized collagen deposition in well-formed granulation tissue in the optimum drug-loaded system. Biochemical, and gene expression analysis showed significant up-regulation of growth factor-related markers namely; VEGF and TGF-ß, and immune-related markers specifically; CCR4 and CD4 + .

Conclusions

Thus, hyaluronic acid-coated silver nanoparticles loaded with vancomycin offer a very auspicious system for skin wound healing purposes.

Graphical abstract

Meropenem is frequently employed empirically to treat both single and polymicrobial infections. In clinical practice, meropenem injections have been shown to induce thrombocytopenia. The main aim of this study was to examine the incidence of thrombocytopenia following administration of a standardized dose of meropenem. This cross-sectional observational study was conducted at a tertiary care hospital from January 1, 2022, to July 15, 2022. This study included 210 patients admitted to intensive care unit. The patient received a typical dose of meropenem depending on age (300–2000 mg) and had no prior medical history of blood dyscrasias. Thrombocytopenia was observed in 59.5% of subjects who were administered a standard dose of meropenem. Absolute thrombocytopenia was noted in 24.7% of the patients, whereas relative thrombocytopenia was detected in 34.8%. Additionally, 41.5% of the participating patients exhibited no alteration in platelet count. Statistical analysis revealed no significant association between sex and meropenem-associated thrombocytopenia (P = 0.522). Meropenem-induced thrombocytopenia didn’t correlate with age in patients undergoing combination therapy (P = 0.586) or monotherapy (p = 0.615). A significant correlation (p < 0.05) was observed between the dosage (300 mg–3 g) and duration of medication use and thrombocytopenia. The odds ratio indicated an elevated probability of patient fatalities in the single therapy group. This study suggests that thrombocytopenia may arise during meropenem treatment, suggesting that it is a potential adverse effect for physicians and pharmacists to consider during therapy.

Background

Bone tissue regeneration based on the use of porous biomaterial scaffolds is considered a promising approach for treating bone defects and fractures healing. A porous alginate scaffold comprising hydroxyapatite nanoparticles loaded with tranexamic acid was formulated. The prepared scaffolds were characterized in terms of the release profile of tranexamic acid and scanning electron microscopy imaging. A cranial bone defect in rabbits (6 defects/3 rabbits/group) was used as a model for the assessment of hemostatic activity of the used scaffolds and the assessment of the bone formation histomorphometrically after its application for 14 days.

Results

The scaffold appeared with irregular porous structure and controlled the release of tranexamic acid over 4 h. The hemostatic time of the medicated and non-medicated scaffolds were 20 and 60 s, respectively. They were significantly lower than the control group (200 s, p < 0.05). The microscopic examination was done after staining histologically prepared sections from the bone defect with Masson trichrome stain and the area % of the newly developed bone was computed. For the medicated group, the new bone area % (75.8 ± 4.9%) was significantly higher than the non-medicated group (58.1 ± 5.9%, p < 0.001). Both groups were significantly larger than the control group that showed bone area % of 43.1 ± 5.6 (p < 0.05). The histomorphometric analysis showed that the medicated scaffold-treated group had more mineralized newly formed bone tissue and smaller amount of soft tissue and residual materials. In contrast, the non-medicated scaffold showed non-mineralized bone cells with larger soft tissue and residual materials.

Conclusion

These results suggested the promising effect of the tranexamic acid-loaded scaffolds in minimizing the time to reach hemostasis by stabilization of the formed hematoma. Additionally, they could improve the quality (mineralization) and the quantity (amount) of the newly formed bone.

Graphical abstract

Background

The effectiveness of conventional oral antiepileptic drug administration is hampered by issues such as inadequate bioavailability, dose-related adverse effects and non-compliance in alleviating epilepsy. Oral antiepileptic drugs have not been successful in treating epilepsy due to high first-pass metabolism, and restriction due to blood–brain barrier and oxidative damage is a significant problem experienced by epileptic patients taking antiepileptic drugs.

The major goal of the current study was to explore the ability of the developed chitosan-coated nanostructured lipid carriers of Oxcarbazepine (CS OXC-NLC) integrated with Vitamin E to lessen oxidative stress and offers neuroprotection and aids in boosting the antiepileptic efficacy through intranasal drug delivery.

Results

In the present work, CS OXC-NLC was fabricated using melt emulsification process. Central Composite Rotatable Design has been utilized to optimize formulation. The study findings showed that optimized CS OXC-NLC exhibited 1.8 times increment in in vitro release and a twofold enhancement in permeability in comparison with the Oxcarbazepine suspension. Confocal microscopy verified the improvement in penetration by showing greater fluorescence in CS OXC-NLC (40 µm) than Oxcarbazepine suspension (22.8 µm) through the nasal mucosa. The pharmacokinetic parameters and biodistribution of OXC levels in the brain and plasma were duly examined. The rise in the amount of drug inside the brain demonstrates the effectiveness of targeting via intranasal administration.

Conclusion

The study outcome demonstrated that the developed CS OXC-NLC is a viable synergistic method producing alluring results for alleviating epilepsy. It depicts the potential of chitosan coating in enhancing the in vivo prospect of the developed formulation through intranasal delivery. Chitosan plays a significant role in enhancing the performance of NLC for intranasal delivery owing to its mucoadhesion properties, controlled release, permeation enhancement and biocompatibility.

Graphical abstract

Background

This study focuses on a fixed-dose combination of lidocaine hydrochloride and diltiazem hydrochloride for the treatment of anal fissures, where lidocaine acts as an anesthetic and diltiazem serves as a slow calcium channel blocker. The objective is to provide a concise overview of the fundamental principles of spectrophotometric and chromatographic methods for quantitative analysis from 2012 to 2022.

Main text

This review highlights the development of novel techniques for both individual and simultaneous quantification, including ultraviolet–visible spectrophotometry (UV–Vis), high-performance liquid chromatography, and high-performance thin-layer chromatography. Additionally, it addresses the capability of various analytical methods to detect and measure compounds at microgram to nanogram levels.

Conclusions

From 2012 to 2022, significant advancements in spectrophotometric and chromatographic methods for analyzing pharmaceutical compounds such as lidocaine and diltiazem have been made. These advancements have improved the sensitivity, accuracy, and efficiency of quantitative analyses, contributing to better quality control and therapeutic efficacy of pharmaceutical products. Modern techniques can detect and quantify compounds at microgram to nanogram levels, ensuring accurate dosing and safety assessments in pharmaceutical formulations.

Background

Osteoarthritis, the most common joint disease, affects over 500 million people globally, especially the elderly. Due to the increasing aging population and obesity rate, obesity is expected to increase over time, making it a significant public health challenge. This study investigated the protective effects of bitter lemon extract against obesity-exacerbated osteoarthritis.

Methods

Thirty male Wistar rats were randomly grouped into six (n = 5). Group 1(control) received 1 ml/100 g water daily. Groups 2–6 were induced in obesity using a high-fat diet. Groups 3–6 were induced with osteoarthritis using 4 mg/kg sodium monoacetate. Group 4 received 40 mg/kg ibuprofen, while groups 5 and 6 received 100 mg/kg and 200 mg/kg Mormordica charantia (MC), respectively, orally for 18 days.

Results

MC Treatment conferred a marked reversal of the cardinal signs of obesity-linked osteoarthritis, restricted inflammatory markers, such as TNF-α and IL-1β, and adipokines, such as leptin. There is also a possible mechanism for MC cartilage protection by suppressing the collagen-damaging enzyme MMP-13, while reversing the cartilage-building block aggrecan suppression.

Conclusion

Current research suggests that bitter melon extract can serve as an alternative therapy for obesity-related Osteoarthritis. Its multi-target actions on inflammation, oxidative stress, and cartilage degradation may offer advantages over the current treatments that focus on symptom relief.