DARU Journal of Pharmaceutical Sciences最新文献

Background: Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability.

Objective: The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety.

Methods: The effect of formulation variables (type of span, SDC % to total lipid content Span/Cholesterol molar ratio) on physicochemical characterization and in vitro drug release in simulated intestinal fluid was investigated. Furthermore, in-vivo protective effect of bilosomes on hepatic and renal functions was also studied.

Results: and conclusion. The results revealed that the best curcumin loaded bilosomal formulation showed spherical nanovesicular morphology with particle size 145.1 ± 19.42 nm with highly reasonable %EE (93%), Zeta potential (≥ -30mv), prominent controlled in-vitro release reaching 55.18 ± 1.10 after 96 h. The formulation also showed good storage stability with negligible differences in physical features and content. The IC50 values of bilosomal, niosomal, and free curcumin were 216.50, 211.44, and 121.63 mmol/ml, respectively revealing that the unencapsulated curcumin displayed high toxicity on Caco2 cell line (nearly 2 folds). Additionally, the prepared bilosomes showed significant in-vivo hepatic and renal protection in liver cirrhosis induced rats with conservation to all liver and renal markers and histopathological morphology. The study assumes the effectiveness and safety of oral delivery of curcumin loaded bile salts stabilized nanovesicles and its powerful commandment for further investigations.

Background: High-performance liquid chromatography (HPLC) has emerged as a highly sensitive and versatile analytical technique for quantifying antihypertensive drugs, such as Captopril (CAP). This study focused on the optimization and validation of an HPLC method for quantifying CAP in an in vitro hydrogel permeability test.

Objectives: The main objective of this study was to develop and validate an HPLC method for quantifying CAP in an in vitro hydrogel permeability test.

Methods: The HPLC method employed a C18 column (Waters, Sunfire, 5 μm; 250 × 4.6 mm) and a mobile phase consisting of methanol-water (85% v/v orthophosphoric acid) in a 55:45 (v/v) ratio at a flow rate of 0.5 mL/min. The UV-Vis detector was configured to detect CAP at a wavelength of 220 nm. The hydrogel film used in the permeability test was prepared using poly (vinyl alcohol)/poly (vinyl caprolactam) (PVA/PNVCL) with citric acid as a crosslinking agent.

Results: All results met the validation parameters according to ICH Guideline. The HPLC method showed consistent retention time (4.7-4.9 min), linearity (1-50 µg/mL; r = 0.9995), accuracy (98.11-101.78%), precision (RSD ≤ 2%), and LoD/LoQ (0.19/0.62 µg/mL). The developed HPLC method was successfully applied to an in vitro permeability test using horizontal diffusion cells. The results demonstrated that CAP permeated through the swollen hydrogel film, with a cumulative drug permeation exceeding 30%.

Conclusion: This highlighted the method's utility in assessing drug transport properties through hydrogels. The validated HPLC method demonstrates robustness and reliability for quantifying CAP in the hydrogel permeability test.

Objectives: Electroceuticals refers to the constantly growing disciplines of bioelectric and bioelectronic medication. These include a broad variety of devices that have been invented and are now being utilized in medical implants, wearable medical electronics, and bioelectronics. The primary aim of this study is to encompass several facets of electroceuticals, their applications, and recent advancements in the field of medical challenges.

Evidence acquisitions: A complete literature study was conducted, which included a comprehensive review of globally recognized scientific research databases.

Results: The progressive refinement and diminution of technology, in conjunction with swift advancements in comprehending the role of electrical pathways in the human body, have rendered it progressively viable to manipulate these pathways for therapeutic purposes.

Discussion and conclusion: Electrical stimulation impacts and modifies biological functioning and pathological processes in the body. In the contemporary era of medicine, health care practitioners from a variety of fields utilize electricity to cure disease or injury or to assess and diagnose using a variety of electrically driven medical tools.

Objective: The main aim of this study was to explore and understand the emerging developments, changes, and patterns shaping the future of the pharmaceutical industry. The pharmaceutical industry is evolving rapidly due to scientific breakthroughs, societal changes, and technological advancements. Companies can adapt, and innovate to stay competitive and advance healthcare objectives by understanding the changes and patterns shaping the future.

Methods: We conducted a thorough Scoping Review across PubMed, Embase, Web of Science, and Scopus, focusing on future trends in the pharmaceutical industry. Studies were carefully selected based on predefined criteria, ensuring a comprehensive and relevant collection.

Results: We identified and selected 24 studies that met our predefined criteria from a pool of 3617 studies. These studies served as the foundation for a detailed exploration of trends within the pharmaceutical industry. This compilation offers a profound understanding of the diverse forces propelling change, including technological advancements, regulatory shifts, evolving market dynamics, and regional nuances.

Conclusions: This research highlights transformative trends such as artificial intelligence, 3D printing, blockchain technology, and digital integration revolutionizing drug discovery, development, manufacturing, and delivery. However, successful implementation hinges on addressing challenges through practical strategies, interdisciplinary collaborations, and region-specific considerations. Future research should explore implementation approaches, facilitating the effective translation of these innovations into tangible healthcare benefits. This forward-looking analysis empowers the pharmaceutical industry to strategically position itself for long-term success in addressing evolving global needs.

Background: Amphotericin B (AMB) is a drug used to treat vulvovaginal candidiasis (VVC), which is a fungal infection affecting the vagina and vulva. Nevertheless, the substance's limited capacity to dissolve in water leads to poor absorption when taken orally, hence diminishing its therapeutic efficacy. In order to address this limitation, β-cyclodextrin (βCD) was used to create AMB in the form of an inclusion complex.

Objective: This study aims to enhance the solubility and bioavailability of AMB by formulating it into an inclusion complex with βCD. Subsequently, we developed dissolvable microarray patches (DMP) as a novel drug delivery system, optimizing the formulation for improved retention, penetration, and controlled release of AMB.

Methods: The stability of the AMB-βCD inclusion complx (IC) structure has been confirmed by employing molecular docking studies. The formulation of DMP involved the incorporation of IC with polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). The mechanical strength, ability to be inserted, and propensity to irritate Amphotericin B-Inclusion Complex-Dissolvable Microarray Patches (IC-DMP) were evaluated by laboratory experiments utilizing the porcine vaginal mucosal layer. Further investigations, such as Differential Scanning Calorimetry (DSC), were performed to assess the physicochemical characteristics of the IC.

Results: The solubility of the pure medication was greatly enhanced up to fourfold by the inclusion complex. The assessment of IC-DMP exhibited exceptional mechanical robustness and insertion abilities, with no indications of discomfort. Among the formulas tested in ex vivo vaginal kinetic experiments, Formula F3 had the most effective retention in the porcine vaginal mucosal layer. It had an AUC value of 208.02 ± 0.33 h.µg/cm³ and the highest C_max value of 20.05 ± 0.06 µg/cm³. Therefore, Formula F3 was the most efficient formula in terms of vaginal drug delivery.

Conclusion: The integration of IC into the DMP system significantly enhances the solubility and bioavailability of AMB, facilitating its absorption in the circulatory system when applied intravaginally for vulvovaginal candidiasis treatment. These promising initial findings support further clinical evaluation of this novel drug delivery system.

Objectives: Cancer drug resistance is a multifaceted phenomenon. The present review article aims to comprehensively analyze the cellular and molecular aspects of drug resistance in cancer and the strategies employed to overcome it.

Evidence acquisition: A systematic search of relevant literature was conducted using electronic databases such as PubMed, Scopus, and Web of Science using appropriate key words. Original research articles and secondary literature were taken into consideration in reviewing the development in the field.

Results and conclusions: Cancer drug resistance is a pervasive challenge that causes many treatments to fail therapeutically. Despite notable advances in cancer treatment, resistance to traditional chemotherapeutic agents and novel targeted medications remains a formidable hurdle in cancer therapy leading to cancer relapse and mortality. Indeed, a majority of patients with metastatic cancer experience are compromised on treatment efficacy because of drug resistance. The multifaceted nature of drug resistance encompasses various factors, such as tumor heterogeneity, growth kinetics, immune system, microenvironment, physical barriers, and the emergence of undruggable cancer drivers. Additionally, alterations in drug influx/efflux transporters, DNA repair mechanisms, and apoptotic pathways further contribute to resistance, which may manifest as either innate or acquired traits, occurring prior to or following therapeutic intervention. Several strategies such as combination therapy, targeted therapy, development of P-gp inhibitors, PROTACs and epigenetic modulators are developed to overcome cancer drug resistance. The management of drug resistance is compounded by the patient and tumor heterogeneity coupled with cancer's ability to evade treatment. Gaining further insight into the mechanisms underlying medication resistance is imperative for the development of effective therapeutic interventions and improved patient outcomes.

The pharmaceutical industry is poised for transformative advancements amid rapid technological developments and rising challenges. This editorial emphasizes the need to incorporate STEM (Science, Technology, Engineering, and Mathematics) disciplines into educational frameworks to prepare future professionals with the diverse skills essential for success. Effective collaboration between scientific knowledge, business acumen, and interdisciplinary teamwork is crucial for navigating the industry's evolving landscape. Innovations in education, such as e-learning, simulation-based training, and gamification, promote critical thinking, adaptability, and creativity in learners. Furthermore, partnerships between academia and the pharmaceutical sector-through internships, mentorships, and joint research-bridge theoretical knowledge with practical application. By adopting STEM-focused educational strategies and fostering strong industry-academic alliances, the next generation of pharmaceutical professionals will be equipped to tackle complex challenges and drive ongoing innovation and excellence within the industry.

Background: The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion.

Objective: This study used 'pathway/gene-set analysis' Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer.

Methods: A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool.

Results: 9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin.

Conclusion: This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.

Background: Glatiramer acetate (GA), a commonly used treatment for multiple sclerosis (MS), requires long-term frequent injections to ensure its effectiveness. This often leads to adverse effects, patient noncompliance, and economic inefficiency.

Objectives: In this study, poloxamer, as a thermosensitive polymer modified by chitosan (CS) and hyaluronic acid (HA), was employed to prepare an in situ forming prolonged release formulation of GA to overcome the problems derived from frequent repeated injections and to enhance the patient compliance.

Methods: The sol-gel formulation was produced through a cold method and optimized using design of experiments. The final product was characterized in terms of gelation time (GT), rheological behaviors, morphological properties, assay, and drug release kinetics.

Results: The in vitro release rate of GA during the first 24 h was quite rapid, but then it continued at a slower rate of 0.05 mg ml^-1h^-1. The in vivo analysis after the subcutaneous injections showed lower levels of IL-5, IL-13, and uric acid (UA) in mice treated with the gel formulation compared with those receiving free GA in the first few days. However, after 10 days, significantly higher concentrations were detected, which continued to increase slowly.

Conclusion: It can be concluded that the designed thermosensitive sol-gel formula is capable of extending the effectiveness of GA and can be considered as a promising sustained release formulation for the treatment of MS.

Background: Patients with cystic fibrosis commonly suffer from lung infections caused by Pseudomonas aeruginosa. Recently, the Levofloxacin (LVF) nebulizing solution (Quinsair®) has been prescribed for the antimicrobial management. The sustained-release (SR) dry powder formulation of LVF is a convenient alternative to Quinsair®. It has the potential to enhance patient convenience and decrease the likelihood of drug resistance over time.

Objective: In this paper, we set forth to formulate and evaluate the potential application of sodium alginate (SA) and sodium carboxymethylcellulose (SCMC) for sustained pulmonary delivery of LVF.

Methods: The spray-dried (SD) LVF microparticles were formulated using SCMC and SA along with L-leucine (Leu). The microparticles were analyzed in terms of particle size, morphology, x-ray diffraction (XRD), in-vitro drug release, and aerodynamic properties. Selected formulations were further proceeded to short-term stability test.

Results: The polymer-containing samples displayed process yield of 33.31%-39.67%, mean entrapment efficiency of 89% and volume size within the range of 2-5 μm. All the hydrogel microparticles were amorphous and exhibited rounded morphology with surface indentations. Formulations with a drug-to-excipient ratio of 50:50 and higher, showed a 24-h SR. The aerodynamic parameters were fine particle fraction and emitted dose percentage ranging between 46.21%-60.6% and 66.67%-87.75%, respectively. The short-term stability test revealed that the formulation with a 50:50 drug-to-excipient ratio, containing SA, demonstrated better physical stability.

Conclusion: The selected formulation containing SA has the potential to extend the release duration. However, further enhancements are required to optimize its performance.