DARU Journal of Pharmaceutical Sciences最新文献

Background: Irritable bowel syndrome (IBS) requires long-term, site-specific therapy. Mebeverine hydrochloride is effective but limited by rapid metabolism and frequent dosing. This study aimed to develop colon-targeted, controlled-release nanoparticles to improve therapeutic efficacy and compliance.

Methods: Nanoparticles were prepared via chitosan-xanthan gum polyelectrolyte complexation and optimized using a Box-Behnken design. Molecular docking predicted strong binding of mebeverine to the muscarinic acetylcholine receptor (-7.4 kcal/mol). Optimized nanoparticles were enteric-coated with Eudragit S100 for pH-dependent colonic release and evaluated through in vitro dissolution and in vivo efficacy in an acetic acid-induced IBS-D rat model.

Results: Optimized nanoparticles showed a mean size of ~ 380 nm, zeta potential + 25 mV, and entrapment efficiency of 95%. In vitro, the enteric-coated formulation resisted gastric pH and released > 95% drug under colonic conditions within 12 h. In vivo, treated rats demonstrated significantly reduced visceral hypersensitivity (AWR score, p < 0.05), normalized intestinal motility (p < 0.05), and improved behavioral outcomes compared to the IBS group. High-dose nanoparticles performed better than the marketed sustained-release capsule.

Conclusion: The chitosan-xanthan gum nanoparticle system enabled sustained, colon-specific delivery of mebeverine hydrochloride with superior therapeutic efficacy in vivo, offering a promising strategy for long-term IBS management.

Background: Bromelain is a proteolytic enzyme obtained from pineapple stems, possessing diverse pharmacological properties such as antioxidant, antidiabetic, anticancer, anti-inflammatory, anthelmintic, cardioprotective, nephroprotective, and antiaging effects. However, its therapeutic potential has been limited due to poor bioavailability and low blood-brain barrier (BBB) permeability.

Objectives: This review aims to summarize the therapeutic effects of bromelain, highlight its pharmacological importance, and discuss novel drug delivery system (NDDS)-based nanoformulations developed to enhance its bioavailability and clinical applicability.

Methods: Relevant literature was reviewed to collect data on bromelain's pharmacological activities, limitations in clinical use, and recent advancements in nanoformulation-based delivery approaches. Additionally, available clinical trial data involving bromelain were examined.

Results: NDDS-based formulations, including solid lipid nanoparticles, gold nanoparticles, silver nanoparticles, nanoemulsions, and nanostructured lipid carriers, have been shown to improve bromelain's bioavailability and BBB permeability, thereby enhancing its therapeutic efficacy. Several clinical studies further support its pharmacological potential, though broader investigations remain limited.

Conclusion: Bromelain exhibits wide-ranging therapeutic benefits, and NDDS-based nanoformulations provide a promising strategy to overcome its pharmacokinetic limitations. Further clinical research is needed to validate its efficacy and establish its role in pharmaceutical and nutraceutical applications. Our evaluation emphasizes that nano-enabled delivery is the most credible route to consistent pharmacokinetics and effect sizes across indications; however, dose-exposure-response data remain sparse and should be prioritized in upcoming trials.

Obesity is a health problem with an economic burden. This study examined the anti-obesogenic impact of caffeic acid (Caf) or resveratrol (Res) and their effect on lipogenic enzymes. Wister albino rats received high-fat diet (HFD) for 16 weeks then were randomly allocated into three groups and treated orally with either drug vehicle, Caf (50 mg/kg/day) or Res (120 mg/kg/day) for further 6 weeks. Rats in control group received normal chow diet for 22 weeks. Treatment of obese rats with either Caf or Res attenuated body weight gain and fat pad mass, and improved hyperglycemia and dyslipidemia. Both drugs promoted adiponectin expression, while decreased tumor necrosis factor-alpha (TNF-α) levels in white adipose tissue (WAT) of obese rats. Res down-regulated the expression of sterol regulatory element binding protein-1 (SREBP-1) mRNA and protein levels of ATP citrate lyase (ACLY) and fatty acid synthase (FAS), to a greater extent than Caf. Conversely, both drugs promoted adipose triglyceride lipase (ATGL)-mediated lipolysis in obese rats and the effect of Res was superior to that of Caf. These findings suggest that Caf and Res have certain regulatory effects regarding obesity-related metabolic disorders, more likely through modulating lipogenesis and lipolysis-related proteins.

Background: Resistance to docetaxel (DTX), a frontline chemotherapeutic agent for prostate cancer (PC), remains a major therapeutic challenge, often driven by impaired apoptosis and enhanced metastatic potential. Calebin A (CA), a natural polyphenol derived from turmeric, has demonstrated anticancer properties in various malignancies. This study investigated the individual and combined effects of CA and DTX on proliferation, apoptosis, cell cycle progression, migration, and gene expression in human PC3 prostate cancer cells.

Methods: PC3 cells were treated with varying concentrations of CA and DTX, alone or in combination. Cell viability was assessed using the MTT assay, and drug interactions were evaluated using the combination index (CI) analysis. Flow cytometry was employed to analyze apoptosis and cell cycle distribution. Gene expression of Bax, Bcl-2, MMP-2, and MMP-9 was quantified using qRT-PCR, while gelatin zymography and wound healing assays evaluated protease activity and migratory behavior, respectively.

Results: Both CA and DTX exhibited time- and dose-dependent cytotoxicity, with combination treatment producing synergistic effects (CI < 1). Co-treatment significantly increased apoptotic cell populations and induced marked sub-G1 and G2/M cell cycle arrest. The combination therapy upregulated the pro-apoptotic Bax/Bcl-2 ratio and downregulated MMP-2 expression, with modest reductions in MMP-2 and MMP-9 enzymatic activities. Furthermore, migratory capacity was significantly diminished under combinatorial treatment compared to monotherapies.

Conclusion: CA enhances the antitumor efficacy of DTX by potentiating apoptosis, inhibiting migration, and modulating gene expression associated with metastasis and survival. These findings suggest CA as a promising adjuvant to overcome chemoresistance and improve therapeutic outcomes in prostate cancer.

Background: Cardiovascular diseases (CVDs) remain the leading cause of death globally, necessitating innovative therapeutic strategies. Nanoparticles have emerged as a promising tool due to their unique properties, including tunable size, high surface area, drug-loading capacity, and the ability to be functionalized for targeted delivery. Their potential in early detection, precise drug delivery, and localized therapy positions them as a transformative approach in CVD management.

Objectives: This review explores the latest advancements in nanoparticle-based interventions for CVDs, focusing on their role in targeted drug delivery, diagnostic applications, and therapeutic efficacy. We highlight how engineered nanoparticles can improve specificity, reduce systemic side effects, and enhance treatment outcomes.

Methods: We examine preclinical and clinical studies on lipid-based, polymeric, and inorganic nanoparticles optimized for CVD treatment. Their surface modifications, drug-release mechanisms, and targeting capabilities are analyzed, with particular attention to their applications in atherosclerosis, myocardial repair, and inflammation modulation.

Results: Functionalized nanoparticles demonstrate significant potential in CVD therapy by enabling site-specific drug delivery to atherosclerotic plaques, damaged cardiac tissue, and inflamed vasculature. Chemical and natural-based nanoparticles show enhanced therapeutic precision, with improved outcomes in drug bioavailability and reduced off-target effects.

Conclusion: Nanotechnology is reshaping CVD treatment through advanced drug delivery systems that enhance precision and efficacy. By leveraging nanoparticle engineering, future therapies can achieve targeted, personalized interventions, offering new hope in combating CVDs.

While traditional peer review offers advantages in academic publishing, it is often hampered by significant weaknesses, leading to frustration among many authors. Scientific discoveries after publication depend on thorough discussions and critiques, making post-publication peer review (PPPR) an essential tool for identifying errors and encouraging authors to make necessary corrections. PPPR is defined as a critical, ongoing, and public review conducted by the broader scientific community once research findings are formally published. Its goal is to enable more academic experts to continuously examine, question, and validate the work, identifying potential flaws or strengths that might have been missed during the initial review. This ongoing dialogue promotes transparency and motivates authors to make necessary corrections. Although the goal of PPPR is to enhance scientific integrity, the open nature of PPPR platforms makes them vulnerable to misuse. It can also be exploited to undermine colleagues, suppress differing viewpoints, or further personal or organizational interests. We also observe an increase in "hyper-skepticism," which differs from constructive criticism, reflecting an overly critical mindset that focuses on doubt rather than fostering understanding. To fully realize the benefits of PPPR and prevent misuse, the scientific community must build a more equitable and more responsible framework. Addressing these challenges requires a thoughtful strategy that integrates technological advancements, strengthens editorial policies, enhances transparency measures, and provides robust protections for good-faith scientific debate.

Background: Tacrolimus is a critical calcineurin inhibitor used in the management of liver transplant recipients. Currently, several pharmaceutical companies have developed and introduced generic formulations of Tacrolimus. Most studies on the use of generic Tacrolimus have focused on the conversion from branded to generic versions in stable patients.

Objectives: The aim of this study is to assess the efficacy and safety of Suprotac® compared to Prograf®, over a 12-month period in de novo adult liver transplant recipients.

Methods: This randomized clinical trial was conducted among adult liver transplant recipients at the Shiraz Transplant Center from October 2022 to June 2024. All patients over 18 years of age, with Tacrolimus as part of their post-transplant immunosuppressive regimen, were included in the study. Patients were randomly assigned to two groups: those receiving Suprotac® and those receiving Prograf® for 12 months in de novo manner. All patients were followed up for 12 months post-transplant. The incidence of rejection, graft loss, liver enzyme fluctuations, safety profile, and adverse events were evaluated between the two groups.

Results: A total of 152 patients participated in this study. The rejection rates were 5.88% in the Suprotac® group and 14.28% in the Prograf® group (p-value:0.093). Mortality rates were 22.05% in the Suprotac® group and 10.71% in the Prograf® group (p-value: 0.056. Additionally, 10 patients experienced graft loss. No significant differences were found between the two groups regarding fluctuations in liver enzymes and renal function. The most commonly reported adverse events in both groups were neurological complications such as headache, and insomnia.

Conclusion: The findings of this study indicate that de novo use of Suprotac®, compared to Prograf®, offers comparable efficacy in preventing rejection and a similar one-year safety profile in adult liver transplant recipients.

Lactose intolerance affects a significant portion of the global population. Among the proposed treatments for the disease, the main strategy is the use of Lactase, beta-galactosidase, and enzyme before consuming dairy products. The beta-galactosidase enzyme loses its activity in the acidic environment of the stomach before reaching the small intestine environment. In this study, a pH sensitive tablet of beta-galactosidase enzyme with local drug delivery was made for the treatment of lactose intolerance through the hydrogel formulation in the core compartment of the 3D-printed shell of the tablet. The tablets were characterized in terms of morphology, chemical interaction, mechanical properties, dissolution test and pharmacopeial physiochemical requirements. The best polymer weight percentages were selected during the 3D printing of the tablet so that less than 11% release of enzyme within 2 h inside the stomach environment (pH = 1.2) and about 100% enzyme release in the intestinal environment (pH = 6.8) within 6 h was achieved. It should be noted that the enzyme release was confirmed by SDS-PAGE. The recovery of the enzyme activity in tablet was 94%, compared to the activity of the free enzyme. SEM analysis showed smooth, uniform, and continuous layers and the results of FTIR analysis showed no covalent interactions between different materials in the manufacturing process. Furthermore, acceptable tolerances were obtained for pharmacopeial tests including weight variation, content uniformity and assay. According to the results, incorporation of hydrogel into melt extrusion-based 3D printing could be used for producing tailored tablets containing beta-galactosidase enzyme amounts with a delayed release formulation and local oral drug delivery to treat lactose intolerance.

Background: Non-Hodgkin lymphoma, a major cancer type, is usually treated with radiotherapy but encounters challenges with resistance and toxicity. Therefore, the treatment of non-Hodgkin lymphoma needs agents to be very effective while protecting healthy cells. Blueberry extract, rich in micronutrients, flavonoids, and bioactive compounds, may inhibit cancer cell growth and induce apoptosis without harming normal cells.

Objectives: This study investigates the efficacy of blueberry extract in combination with radiotherapy as a radiosensitizer on Raji cells, a model for highly invasive non-Hodgkin lymphoma.

Methods: First, Raji cells were treated with blueberry extract alone and in combination with a single dose of 2 Gy radiotherapy. The effects of blueberry extract on inhibiting proliferation and induction of apoptosis in Raji cells were investigated by MTT assay, flow cytometry (Annexin-V-FITC), cell cycle analysis, and quantitative gene expression analysis of BAX, BCL-2 and XPA. Its role in improving the efficacy of radiotherapy on cancer cells was also investigated.

Results: Treated cells with blueberry extract alone and in combination with radiotherapy showed reduced viability, increased induction of apoptosis and a higher proportion of cells in the SUB-G1 cell cycle phase was detected. Additionally, gene expression analysis indicated upregulation of the pro-apoptotic gene BAX expression and decreased anti-apoptotic gene BCL-2 expression, along with elevated expression of XPA as an indicator of DNA damage after radiotherapy.

Conclusion: The study suggests that blueberry extract stimulates apoptosis in Raji cells and could serve as an anti-cancer drug. Furthermore, the combination of this extract with radiotherapy could be used as a radiosensitizer.

Enhancing the bioavailability of insoluble active agents in the eye through topical administration is a key focus in formulation science. This study aims to develop a microsuspension-based drug delivery system to effectively deliver anti-inflammatory drugs to deeper ocular tissues, offering a non-invasive alternative to intraocular injections.

Methods: To improve the bioavailability of the hydrophobic drug triamcinolone acetonide (TA), we reduced its particle size using the wet ball milling method with zirconium oxide beads. To enhance mucus penetration, we coated the TA microsuspension with the non-ionic surfactant Poloxamer 407. The microsuspension was characterized for morphology, particle size, zeta potential, and dissolution properties in various ocular media. We also modeled TA distribution in different ocular compartments using GastroPlus™ software and evaluated the impact of formulation parameters such as particle size and viscosity.

Results: Reducing the particle size to 250 nm significantly increased the dissolution rate of the microsuspension. The model indicated that viscosity and particle size are critical for enhancing the ocular concentration of eye drops in various tissues. Optimizing these parameters could lead to a nearly 40-fold reduction in the required TA eye drop dosage (from 4.0% w/v to 0.1% w/v).

Conclusion: Our findings suggest that a TA formulation with a particle size of 1.0 μm or less and a viscosity of about 72.0 cp. can be as effective as a larger particle size formulation while delivering significantly higher TA concentrations. The enhanced uniformity, re-dispersibility, and improved distribution to ocular tissues position this microsuspension as a novel approach to overcoming ocular drug delivery challenges and reducing the need for intraocular injections.