Future Journal of Pharmaceutical Sciences最新文献

Background

The oral route is the recommended route of administration of most therapeutic drugs. Unfortunately, due to swallowing difficulties especially for elderly and young patients, conventional oral dosage forms have low patient compliance. To overcome these difficulties, orally disintegrating tablets (ODTs) were presented in this work.

Results

In this study, the solubility of rivaroxaban (RXB) was enhanced using nano mixed micelles (NMMs). The optimum NMM formula was selected according to the highest drug content (8.00 ± 0.02 mg), clarity upon reconstitution, smallest particle size (PS) (161.50 ± 2.50 nm), lowest polydispersity index (PDI) (0.37 ± 0.01), and optimum zeta potential (ZP) (− 16.13 ± 0.42 mV). The optimized formula was then mixed with different ODT carriers (gellan gum, sodium alginate, and hydroxypropyl methylcellulose) and freeze dried. The ODTs were evaluated via weight variation, thickness and diameter, friability, drug content, in vitro disintegration, swelling profile, in vitro dissolution. The tablet containing 35 mg sodium alginate (SA) and 15 mg gellan gum (GG) was found to fulfill the optimum criteria for ODTs. The in vitro disintegration profile of tablets was evaluated in six human volunteers, revealed a disintegration time ranging from 31.5 ± 1.89 s to 85 ± 3.54 s.

Conclusion

A promising ODT formulation containing RXB-loaded NMMs has been successfully developed, offering a suitable option for special populations such as the elderly and children who experience difficulty swallowing. This advancement may enhance treatment effectiveness by improving patient compliance.

Nanoparticles have gained prominence in the formulation of nanopesticides, leveraging their unique nanocharacteristics. This study delves into the nephrotoxic implications of CuONanoSheet (CuONS), as nanopesticide tailored for agricultural applications to understand its safety and viability in this field. The nanocharacterization of CuONS was meticulously examined using X-ray diffraction, high-resolution transmission electron microscopy, field emission scanning electron microscopy and Zeta-Sizer device, which assessed zeta-potential, hydrodynamic size, and polydispersity index. Rats treated with CuONS showed elevated levels of blood urea nitrogen, creatinine, and uric acid and a significant increase in lipid peroxidation (MDA) and reduced levels of antioxidant enzymes. CuONS treatment resulted in an imbalance in pro-apoptotic Bax and anti-apoptotic B-cell lymphoma2 (Bcl2) levels. Histologically, CuONS induced glomerulus degeneration and vacuolation in tubules lining epithelium. Immunohistochemical evaluations revealed strong expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor-alfa (TNF-α), and the tumor suppressor gene (p53) in CuONS-treated kidneys. Ultrastructural assessments further confirmed these structural abnormalities. While CuONS exhibits potential as a nanopesticide, caution is warranted due to observed negative impacts on kidney functions, and histological architecture, in this study. Careful consideration of potential side effects on other living organisms is imperative in the utilization of CuONS in agricultural practices.

Background

Ebola virus (EBOV) causes severe hemorrhagic fever outbreaks with high mortality rates, and currently there are no approved antiviral drugs. In this study, in silico (computational) techniques were applied to evaluate six small-molecule inhibitors—Latrunculin A, LJ001, CA-074, CA-074Me, U18666A, and Apilimod—focusing on drug-likeness, ADMET profiles, molecular docking, quantum chemical descriptors, and molecular dynamics simulations.

Results

Among the tested compounds, CA-074 proved to be the most promising candidate as it exhibited strong binding affinity to Cathepsin B (− 40.87 kcal/mol), an endosomal cysteine protease crucial for Ebola virus entry, as well as favorable ADMET properties and safety indicators such as absence of the human Ether-à-go-go-Related Gene (hERG) inhibition and mutagenic potential. CA-074 fulfilled the Lipinski and Veber rules with low plasma protein binding and a high unbound fraction, indicating improved bioavailability. The quantum descriptors indicated high chemical stability and low reactivity. Molecular dynamics confirmed the stability of the CA-074–Cathepsin B complex over 300 ns, with persistent hydrogen bonds and low flexibility in the binding pocket.

Conclusion

CA-074 has the potential to be a leading candidate for the treatment of EBOV. The comprehensive in silico strategy provides a valuable framework for accelerating early-stage antiviral drug discovery.

Background

Hepatocellular carcinoma (HCC) represents 90% of primary liver cancers and is the fourth leading cause of cancer-related death worldwide. Sorafenib remains the standard first-line systemic therapy for advanced HCC, though real-world outcomes vary from clinical trial results. We aimed to evaluate survival outcomes and identify prognostic factors in HCC patients receiving sorafenib in routine clinical practice over an 18-month follow-up period in a real-world clinical setting.

Methods

An ambispective cohort study (integrating retrospective and prospective data) was conducted involving 347 patients with confirmed primary HCC treated with Sorafenib between June 2023 and January 2025, of whom 292 had complete 18-month follow-up and were included in the survival analysis. Clinical data, laboratory markers, imaging Response Evaluation Criteria In Solid Tumors (RECIST 1.1), adverse effects, and treatment modifications were analyzed. Kaplan–Meier analysis and Cox regression models were used to determine overall survival (OS), progression-free survival (PFS), and prognostic predictors.

Results

The observed OS rates at 6, 12, and 18 months were 69.3%, 45.2%, and 31.1%, respectively. Corresponding PFS rates were 58.6%, 36.9%, and 24.8%. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status ≥ 1, AFP > 400 ng/mL, Albumin-Bilirubin (ALBI) grade 3, and vascular invasion were significantly associated with reduced OS (p < 0.05). Patients who achieved partial response or stable disease per RECIST were more likely to continue Sorafenib beyond 6 months. Toxicity was generally tolerable, with a low rate of permanent treatment discontinuation.

Conclusion

Sorafenib continues to demonstrate efficacy in real-world practice as first-line therapy for advanced HCC, with clear clinical and biochemical indicators, including ALBI grade, AFP, ECOG, and early radiological response, serving as key prognostic factors of treatment success. Early response assessment with identification of poor prognostic factors is critical for optimizing outcomes, and proactive toxicity management can improve outcomes in real-world settings.

Background

The efficacy of synthetic drugs in the treatment of diabetes mellitus often falls short, limiting their use to symptom management. Consequently, there has been an increasing fascination with alternative medicine, specifically herbal remedies. The presence of alkaloids in medicinal plants presents a promising prospect for the advancement of novel approaches to diabetes mellitus therapies. The aim of this research is to evaluate the bioactive alkaloid phytoconstituents and their interaction with the α-amylase and α-glucosidase inhibitors using in-silico approach.

Results

A total of 49 phytoconstituents were analyzed as potential inhibitors of these enzymes with top 15 selected based on molecular docking studies. Physicochemical properties, ADME (absorption, distribution, metabolism, and excretion) profile, and toxicity predictions were performed to predict pharmacokinetics, drug-likeness, and toxicity. Subsequently, the molecular docking study was performed using Schrodinger software (PDB ID: 3TOP). Piperumbellactam C (− 8.18 kcal/mol) and Trigonelline (− 7.99 kcal/mol). displayed the highest docking score and standard acarbose showed (− 8.97 kcal/mol). The MM-GBSA (Molecular Mechanics, General Born Surface Area) assay showed favorable binding energy. All other phytoconstituents exhibited favorable pharmacokinetic and toxicological parameters and found within acceptable ranges. Further, a 200 ns MD (Molecular Dynamic) Simulation study was carried out in order to check the stability of Piperumbellactam C-3TOP complex.

Conclusions

The findings of this research validate the antidiabetic properties of some active alkaloid phytoconstituents and additionally showcase the potential inhibitory activity via in-silico analysis.

Background

Today brain tumors are the most life-threatening diseases which universally have a high death rate and reported as a second leading cause of death in not only adults but also children. Several medicinal approaches have been utilized to treat tumors, but the recommended methods had some limitations. Numerous phytoconstituents isolated from various medicinal plants have been reported to have anticancer property, but there are some major reasons for the clinical failure of these compounds such as its poor solubility, bioavailability and tissue distribution and poor absorptivity in the body. Thus, there is a strong need to design the best treatment to cancer cells with great efficiency, less side effects and with promising approach for the delivery strategies. Nanotechnology is proved to be a bridge to overcome the limitation of conventional therapies of drug administration and distribution in the cancer treatment. In the present study, curcumin- and 6-gingerol-based nanoemulsion (CGNE) has been successfully develop and characterized.

Result

The FTIR spectroscopy of CGNE exhibits typical spectra of both curcumin and 6-gingerol. The pH of CGNE was found to be acidic, and the refractive index value of formulated CGNE was found to be 1.38, indicating the isotropic nature of drugs. Percentage transmittance of nanoemulsion was close to 100%. Zeta potential of optimized nanoemulsion was found to be –29 mV. During ex-vivo drug diffusion studies, 48.4% and 78% diffusion of curcumin and 6-gingerol, respectively, were observed from CGNE at the end of 6 h, and followed the anomalous release mechanism.

Conclusion

The drug release mechanism of the formulated CGNE was calculated by using the Korsmeyer–Peppas equation, and the diffusion exponent ‘n’ for curcumin and 6-gingerol indicated the anomalous release mechanism. In vitro cytotoxicity against the human glioblastoma cell line U373-MG, study demonstrated that the combination of curcumin- and 6-gingerol-based nanoemulsion showed the synergistic result of cell growth inhibition.

Background

Diabetes mellitus is a multifactorial metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion and/or action. Oxidative stress, impaired insulin signaling, and dysregulated glucose transport are central to its pathogenesis. Given the limitations and side effects of current pharmacotherapies, attention has shifted toward natural compounds with multitargeted mechanisms of action.

Purpose of the study

This study aimed to explore the antidiabetic potential of Chamazulene (Cham) and Cinnamic Acid (CA), natural bioactive compounds, through in silico and in vivo approaches, targeting key molecular pathways including IRS2/GLUT4, HNF4α, and GLUT2, as well as assessing their effects on oxidative stress, DNA integrity, and lipid metabolism.

Methods and results

Male Wistar rats were assigned into eight groups: three control groups (C, C+Cham, C+CA) and five streptozotocin-induced diabetic groups (DM, DM + Cham, DM+CA, DM+Cham + CA, and DM+Gli. Our study highlighted the inhibitory α-amylase effect of both nutraceuticals. Biochemically, DM+Cham+CA surpassed the single treatments effects on lowering blood glucose, improving lipid profile, balancing redox system evidenced by improving GPx and GR activity. Moreover, using flow cytometry and Comet test, the used treatments extended their beneficial effects to inhibit reactive oxygen species and DNA damage, respectively. Using qRT-PCR, the treated groups upregulated skeletal muscle IRS2, GLUT4 gene expression, downregulated hepatic GLUT2 and HNF4α. Notably, natural compounds outperformed the standard drug in several parameters.

Conclusion

The findings support the therapeutic promise of Chamazulene and Cinnamic Acid as natural alternatives or adjuncts to conventional antidiabetic drugs. Further studies involving diverse models and clinical validation are warranted to confirm efficacy and safety in humans.

Background

Cancer remains a major global health burden, contributing significantly to illness and death worldwide. Although current treatments such as chemotherapy, radiation therapy, and surgery have improved patient outcomes, they are frequently limited by severe side effects, drug resistance, and damage to healthy tissues. These challenges have prompted the search for novel, safer, and more targeted therapeutic options.

Main body

Rhamnetin, a naturally occurring compound found in various plants, has emerged as a promising candidate in cancer therapy due to its diverse range of biological activities. It has demonstrated the ability to induce programmed cell death in cancer cells, inhibit the formation of new blood vessels that support tumor growth, and prevent the transition of cancer cells to more invasive forms. Rhamnetin also regulates oxidative stress and mitochondrial function, contributing to its anticancer effects. Notably, it appears to preferentially affect cancerous cells while minimizing harm to normal tissues, suggesting a more targeted therapeutic profile. In addition to its individual therapeutic properties, rhamnetin has shown potential in enhancing the effectiveness of conventional treatments. By sensitizing cancer cells to existing therapies, it may help overcome resistance and improve overall treatment outcomes. Despite these promising effects, its clinical application remains limited by poor absorption, rapid metabolism, and low bioavailability. Recent advancements in drug delivery systems, including the use of nanoparticles and liposomes, offer promising strategies to address these limitations. These technologies have the potential to improve the stability, absorption, and targeting of rhamnetin, thereby enhancing its therapeutic value.

Conclusion

Rhamnetin represents a compelling natural compound with significant anticancer potential. Its ability to selectively target cancer cells, modulate multiple cancer-related pathways, and improve the efficacy of conventional treatments positions it as a valuable candidate for future cancer therapies. Continued research into optimized delivery methods and clinical applications is essential to fully harness its benefits in cancer treatment.

Background

Hypoxia has been recognized as a major contributor to cancer progression. Targeting hypoxia-derived factors, particularly in breast cancer, may present an auspicious strategy for cancer therapy. Honey-derived natural products have demonstrated therapeutic potential for various ailments, including cancer. However, research on their effects under hypoxic conditions remains limited. This study aims to elucidate the potential of honey-derived natural products as anticancer agents for breast cancer under hypoxic conditions. An integrative bioinformatics approach was employed, including drug-likeness screening, toxicity analysis, differential gene expression analysis, gene and protein enrichment analysis, immune infiltration correlation analysis, molecular docking, and molecular dynamic simulations.

Results

Five potential compounds with favorable drug-like properties and minimal toxicity effects were identified, including 2,2-dimethyl-8-prenylchromene, chrysin, galangin, kaempferol, and pinobanksin. These compounds were further assessed for their ability to target hypoxia-associated factors. Public database analysis revealed that N-myc downregulated gene-1 (NDRG1) is significantly upregulated in breast cancer under hypoxic conditions. Enrichment analysis demonstrated that elevated NDRG1 expression is strongly associated with poor patient outcomes. Interestingly, high NDRG1 expression is correlated with immune cell infiltration, including monocytes, myeloid-derived suppressor cells, and neutrophils, which are known components of the tumor microenvironment that promote cancer progression. Molecular docking results indicated that chrysin exhibited a more favorable binding affinity than other compounds, including the control drug Combretastatin A-4. Moreover, a 100-ns molecular dynamics simulation demonstrated that chrysin exhibited dynamic behavior comparable to the control drug across nearly all measured parameters, suggesting its potential as an anticancer agent.

Conclusion

These findings highlight the promise of chrysin as a candidate for breast cancer treatment under hypoxic conditions by targeting NDRG1. Further experimental validation is warranted to support its development as a therapeutic agent.

Background

Acute kidney injury (AKI) and chronic kidney disease (CKD) pose significant global health challenges, often worsened by the use of certain therapeutic agents and exposure to environmental toxins. This review aims to explore the nephroprotective role of botanicals, specifically focusing on the damage to kidneys caused by prolonged use of modern medicines and environmental toxicants.

Main body of the abstract

This review provides a detailed overview of Traditional Indian Medicinal Plants (TIMP), highlighting their botanical components and the potential mechanisms through which they offer nephroprotection in cases of chronic kidney disease. The analysis includes existing research studies on the nephroprotective effects of these plants, particularly in the context of both acute and chronic kidney diseases. Findings suggest that botanicals derived from TIMP hold promising potential for developing nephroprotective therapies.

Short conclusion

Research has shown that TIMP can effectively reduce kidney damage induced by various nephrotoxic agents, as evidenced by studies on animal models. Some of the TIMP with notable potential for treating chronic kidney disease include Camelia sinensis (L.), Nigella sativa (L.), Andrographis paniculata (Burm.f.), Daucus carota (L.), Foeniculum vulgare (L.), Glycyrrhiza glabra (L.), and Cucumis sativus (L.).

Graphical abstract