Future Journal of Pharmaceutical Sciences最新文献

Background

To investigate medicinal plants used in the traditional treatment of cutaneous leishmaniasis using multivariate tests coupled with pharmacokinetic predictions in silico.

Main body

Interviews were conducted with 21 herbalists in Annaba and El Tarf provinces. The dataset comprised 26 variables, and multidimensional analyses were applied using the FactoMineR package. Nineteen species were reported in this survey. Among them, the most important family was Lamiaceae, with five species. According to the RFC index, the most famous species were the aerial parts of Teucrium polium L. (57.14%).

Second, a data matrix for the species generated showed higher contribution values in the first dimension owing to the lack of the topical administration form, the presence of preparation mode by decoction and cataplasm, and the association of medicinal plants specifically with olive oil and honey, respectively. The analysis of the first dimension demonstrated a high association for the form of administration and the mode of administration, with correlation ratios η² of 6.261E-01, 5.501E-01, and 4.772E-01 (p < 0.05), respectively. The cluster analysis identified three clusters differentiated by the administration form per os with a p-value of 7.49E-05 (p < 0.05). Later, the ADME profile was tested in silico by identifying the physicochemical properties of the major compounds reported in the literature.

Conclusions

The results showed that the major compounds of plants with high RFC showed excellent ADME profiles, with good absorption, low toxicity, and favorable distribution, making them promising candidates for the safe treatment of leishmaniasis.

Background

The conventional drug delivery devices always present a “one-size-fits-all” approach which limits their application in pharmaceutical industry, because of their inability to adapt to individual pharmacokinetic features. Three-dimensional (3D) printing is the most economical substitutes for transferring from the “one-size-fits-all” approach (i.e., mass production) to fabricate small individualized batches.

Main text

3D printing, advanced by the additive manufacturing technology, has gained growing demanding and popularity to develop pharmaceutical dosage forms and medical devices; and offered much more preferences over the traditional fabrication technologies. This advanced technology presents the ability of fabricating customizable design, 3D structures with sophisticated architecture, intended for personalized treatment. As a further advancement, the emergence of four-dimensional (4D) printing extensively contributed to the advancement of personalized medication by combining the benefits of smart multiple functional materials with the 3D printing technology. In spite of all of the offered notable progresses in both techniques, some regulatory issues, scalability, and production cost present key obstruction.

Conclusions

In the present article, an overview on the latest research articles demonstrating some step forward accomplishments for exploiting 3D and 4D printing technologies in developing advanced pharmaceutical dosage forms, medical devices, and tissue engineering as well as presenting the foremost challenges and future perspectives.

Graphical abstract

Background

Cardiac remodeling post-myocardial infarction contributes to adverse outcomes and increased mortality. We aimed to evaluate the impact of Dapagliflozin on remodeling markers, clinical outcomes and quality of life of diabetic ST-elevation myocardial infarction (STEMI) patients. This was an open label, single centered, randomized controlled-clinical trial was conducted at the Cardiology department, Ain Shams University. Eligible diabetic STEMI patients (n = 54) were randomly allocated to receive either 10 mg of dapagliflozin plus standard of care (Test group) or standard of care alone (Control group) for 4 weeks. The primary outcome was to assess the changes in suppression of tumorigenicity 2 (sST2) over time. Secondary outcomes included: echocardiographic evaluations (left ventricular ejection fraction (LVEF), End Diastolic Diameter (EDD), End systolic volume (ESV), End diastolic volume (EDV) and quality of life using EQ-5D-5L questionnaire.

Results

No change was observed in sST2 levels either between or within groups from baseline to 4 weeks. Echocardiographic and quality of life parameters were comparable between groups after 4 weeks. LVEF was significantly increased in the study group at the end of study (42 vs. 47, P < 0.001).

Conclusions

Early administration of dapagliflozin in post-MI diabetic patients had no effect on sST2 and quality of life but improved LVEF after 4 weeks of follow up. More studies are needed with larger sample sizes to further investigate SGLT2-inhibitors potential benefits in such population.

ClinicalTrial.gov registration number: NCT05335629

Neurodegenerative disorders, a group of diseases such as Alzheimer’s and Parkinson’s diseases, are identified by gradual memory and motor impairment, thus, seriously affecting aging populations. New research brings a paradigm shift in the pathogenesis of these conditions by identifying gut microbiota as a fundamental factor owing to dysbiosis through microbiota-induced neuroinflammation. Besides, the gut microbiome, referred to as dysbiosis, is exclusively responsible for activating the immune system thereby causing neuroinflammation, something that leads to breakdown of the blood–brain barrier and accumulation of toxic protein aggregates, such as amyloid-beta and alpha-synuclein. The gut-brain axis stays in the way of the advancement of such diseases, provided it allows for the necessary biochemical and immunity links. Microbial short-chain fatty acids (SCFA) and other metabolic by-products that are produced by these microbes either increase or decrease the stability of the central nervous system, while reduced SCFA production caused by dysbiosis, however, brings about neuroinflammation. From this perspective, the microbiota-gut-brain connection serves as a novel source for innovation in disease cure, including probiotics, prebiotics, dietary modifications, as well as the microbiota fecal transplant, restoring the microbial balance and thus, alleviating the disease progression. This examination establishes the current role of the microbiota in neurodegeneration and potential microbiome-focused treatments for neuroprotection.

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.