Journal of Pharmaceutical Innovation最新文献

Purpose

Osteoporosis is a skeletal disorder marked by decreased bone mass and microarchitectural deterioration, which increases fracture risk and reduces quality of life, especially in elderly people. Ananas comosus (pineapple), a tropical plant rich in bioactive compounds, has promising therapeutic potential but remains underexplored for treating osteoporosis. Current pharmacological treatments, although effective, often come with significant side effects and high costs, highlighting the need for safer, more affordable alternatives. Therefore, this study aims to assess the osteoprotective effects of a hydroalcoholic extract of Ananas comosus fruit in a dexamethasone-induced osteoporosis model using female Wistar rats.

Methods

Osteoporosis was induced via intramuscular administration of dexamethasone (7 mg/kg/week for four weeks). Rats were subsequently treated with hydroalcoholic extract of fruits of A. comosus at 200, 400, and 800 mg/kg/day for 15 days. Sodium alendronate (0.2 mg/animal/day) served as the standard comparator. Bone morphometry, bone mineral density (BMD), ash value, serum alkaline phosphatase (ALP), and biomechanical strength were assessed.

Results

Dexamethasone significantly impaired bone health by reducing femur length, thickness, weight, BMD, and ash content, while increasing serum ALP levels (P < 0.001). Treatment with A. comosus extract, especially at 800 mg/kg, led to significant improvements in bone morphometric indices (P < 0.05), restored BMD (P < 0.01), increased ash content (P < 0.01), and decreased ALP levels (P < 0.01). Biomechanical strength was notably improved in the extract-treated groups, nearly matching the effectiveness of sodium alendronate.

Conclusion

A. comosus extract demonstrated dose-dependent anti-osteoporotic effects, which may be attributed to its flavonoids, phenolics, and other phytoconstituents with anti-inflammatory, antioxidant, and osteogenic properties. These findings support its potential as a safe, plant-based therapeutic candidate for glucocorticoid-induced osteoporosis.

Purpose

To develop and evaluate a novel chitosan-coated submicron emulsion (SubE) incorporating a ciprofloxacin-potassium sorbate (CIF-PoS) ionic complex for improved ocular drug delivery, addressing limitations of conventional eye drops such as poor corneal retention and bioavailability.

Methods

The CIF-PoS complex was prepared via ion-pairing at optimized molar ratios and pH, characterized by ¹H NMR. SubEs were formulated using high-energy emulsification with egg lecithin, Pluronic F-68^®, and chitosan. Physicochemical properties (droplet size, zeta potential, viscosity, encapsulation efficiency) were assessed. In vitro release was studied via dialysis. Ex vivo antimicrobial efficacy against Pseudomonas aeruginosa biofilms was evaluated using MIC/MBC assays. In vivo corneal retention was examined in Wistar rats using fluorescence microscopy and HPLC-MS for pharmacokinetics. Stability was tested per ICH guidelines.

Results

The optimized SubE-CN-CIF-PoS exhibited a droplet size of 227.1 ± 5.6 nm and a polydispersity index (PdI) of 0.24 ± 0.03, + 33.2 mV zeta potential, 91.43% encapsulation efficiency, and sustained release (78% over 24 h). It showed comparable MIC (0.0051 µg/mL) and MBC (0.0114 µg/mL) compared to marketed CIF formulations (MF). In vivo, it maintained therapeutic corneal levels for 12 h (20.9% higher than controls). Stability was robust over 6 months.

Conclusion

This biomimetic system enhances corneal adhesion, penetration, and antibacterial action, offering potential for reduced dosing frequency and improved outcomes in ocular infections. No trial registration required as this is preclinical research.

Purpose

Imidazo[1,2-a]pyridine is a pivotal fused heterocycle in medicinal chemistry, widely recognized as a foundational scaffold due to its diverse biological and therapeutic applications. The need for efficient, sustainable, and high-yielding synthetic methodologies for imidazo[1,2-a]pyridine derivatives continue to drive research interest in this domain.

Methods

The present study focuses on developing a highly efficient and sustainable synthetic strategy for imidazo[1,2-a]pyridine derivatives with improved yield and broad applicability. A multistep reaction pathway was employed using readily available starting materials, followed by structural confirmation of the synthesized compounds through FTIR, ¹H NMR, ¹³C NMR, and mass spectrometry analyses.

Results

The optimized reaction conditions yielded products in excellent yields ranging from 91% to 98%, demonstrating superior efficiency, enhanced purity, and high scalability compared to conventional methods. Furthermore, molecular docking studies were performed to evaluate the binding affinity of the synthesized derivatives toward the target protein, revealing significant interactions with key active-site residues that support their potential biological relevance. Drug-likeness assessment based on Lipinski’s Rule of Five confirmed that all compounds exhibited acceptable physicochemical properties, indicating good oral bioavailability and favorable pharmacokinetic profiles. In this approach, alternative coupling systems such as DMTMM and greener solvents (MeCN, 2-MeTHF) are also discussed for further improving the sustainability profile.

Conclusion

Overall, this novel synthetic approach provides a reliable, eco-efficient, and versatile route for the formation of imidazo[1,2-a]pyridine frameworks and holds strong potential for future applications in medicinal chemistry and pharmaceutical development.

Purpose

This study aimed to use response surface methods to create and optimize a ferulic acid (FA)-transferosome (FATF)-based gel (FATF-G). The goal of the study was to create FATF-G in order to get improved photoprotection against UVA radiation.

Methods

FATF was prepared by the thin-film hydration technique and optimized by response surface methodology (RSM). Optimized FATF composed of 20 mg (phospholipid, soy lecithin, SL), Tween 80 (5 mL), and sonication duration (20 min) with solvent chloroform and methanol (2:1, v/v). Entrapment efficiency (%EE), ex vivo skin permeability, solubility, TEM, FTIR, UV, Zetasizer, and stability tests were used to characterize FATF. FATF-G, FACG, and FAPL-G were checked for their photoprotective efficacy and membrane permeability in a rat model.

Results

FATF produced the highest %EE of 99.48 ± 0.54%. Compared to FACG, FATF-G has demonstrated a considerably stronger photoprotection effect (^***P < 0.01), superior permeability (92.08 ± 0.86%), and longer release over 24 h. The FATF-G’s improved drug absorption through skin is possible because FATF had a better permeation coefficient [Kp 4.73 ± 0.07 (cm/h)] and greater solubility (8137.12 ± 1.10 µg/mL) as compared to others. Skin antioxidant defense systems such as GPX, GRD, CAT, MDA, GSH, SOD, and carbonyl protein were significantly elevated by FATF-G (^***P < 0.01) against UVA.

Conclusion

FATF-G, the optimized gel formulation, considerably outperformed FACG in terms of skin permeability and photoprotection activity (^***P < 0.01). Thus, this novel gel system of FA may have the potential for topical delivery to get enhanced therapeutic efficacy and photoprotection against harmful ultraviolet lights.

Graphical Abstract

Breast cancer remains one of the most prevalent malignancies among women worldwide, underscoring the urgent need for safer and more effective therapeutic agents. This study investigates the potential anti-breast cancer properties of bioactive compounds derived from Polyalthia bullata King using an integrative computational and experimental approach. Sequential solvent extraction with solvents of varying polarities was employed to maximize the diversity of phytochemicals extracted from P. bullata. The major bioactive constituents were identified through ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF/MS) analysis. The identified 130 compounds underwent ADMET-based screening to predict their drug-likeness and pharmacokinetic profiles. Drug-like 8 compounds were further explored through network pharmacology to predict potential breast cancer-related targets and involved signaling pathways. From this, 30,453 breast cancer-associated targets were retrieved from the GeneCards database, and 1,619 compound-related targets were identified via SwissTargetPrediction and SuperPred. Protein-protein interaction (PPI) network analysis revealed 646 overlapping targets. Subsequent Gene Ontology (GO) and KEGG pathway enrichment analyses highlighted the hsa05200: Pathways in cancer as a central mechanism, involving key proteins such as AKT1, GAPDH, and IL6. Molecular docking studies identified myricetin, bowdichione, and 4-methyl-1 H-benzo[g]quinoline-2,5,10-trione as top candidates with strong binding affinities toward AKT1. These findings were further validated through molecular dynamics (MD) simulations, principal component analysis (PCA), free energy landscape (FEL) analysis, and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) calculations, all of which confirmed the stability and favorable binding of the compounds to the target protein. Overall, this study suggests that P. bullata-derived compounds, particularly myricetin, bowdichione, and 4-methyl-1 H-benzo[g]quinoline-2,5,10-trione, hold promise as potential therapeutic agents against breast cancer and warrant further experimental investigation.

Aloe vera (L.) Burm.f. (A. vera) is widely recognized for its medicinal properties, yet the therapeutic potential of its flowers remains underexplored. This study investigates the phytochemical compounds and pharmacological relevance of A. vera flowers to identify novel plant-based therapeutic agents. Phytochemical exploration studies of A.vera were done by subjecting it to Soxhlet extraction process and phytochemical screening was carried out using 18 tests which detected various constituents like alkaloids, flavanoids, terpenoids, saponins, tannins, glycosides, anthraquinones, diterpenes. Zonal inhibition activity of A.vera flower extract showed a very strong antimicrobial activity against Listeria monocytogenes, Salmonella typhi, Escherichia coli, Bacillus subtilis, Staphylococcus aureus. LC-MS was carried out to identify the bioactive compounds present in flower extract. Toxicity and carcinogenicity was confirmed by ADMET profile and screened on the basis of acceptance of Lipinsky, Pfizer, GSK. Golden triangle, Ghose, Veber, Egan, Muegge, QED & NP score. Four phytochemical compounds were shortlisted out of 8 based on the ADMET profile which were subjected to Molecular Docking with the Protein PDB id:108A coupled with Human ACE. Among these, tschimganin demonstrated strong binding energy affinity score (-9.5 kcal/mol) and was subjected to Molecular Dynamic simulation, which confirmed the stability of the compound supporting its potential as a lead compound. These findings highlight A. vera flowers as a promising source of bioactive compounds with therapeutic potential. Tschimganin shows strong molecular interaction and stability, suggesting its viability for the development of pharmaceuticals. Other compounds such as seneciphyllin (-9.2 kcal/mol) and cianidanol (-8.7 kcal/mol) were found to be effective as they exhibited several therapeutic applications, including antioxidant, anti-inflammatory, neuroprotective, anticancer, and neural toxicity prevention properties. These phytochemical bioactive compounds present in A.vera flower such as Tschimganin, 8-Hydroxy-13,14,15,16-tetranor-12-labdanoic acid, seneciphyllin, cianidanol, are neither present in A. vera leaf nor gel, so this significant/novel finding of the compounds reported paves the way as promising bioactive agents for therapeutic purposes.

Purpose

The primary purpose of this study is to investigate whether low-cost thermal imaging, combined with optimized deep learning techniques, can provide an accurate, safe, and non-invasive solution for the automated diagnosis and therapeutic monitoring of respiratory diseases. Specifically, the research addresses the question of whether thermal patterns associated with lung inflammation can be effectively learned and discriminated to reliably classify COVID-19, pneumonia, and healthy cases, while maintaining high diagnostic accuracy and model interpretability suitable for resource-limited clinical settings.

Methods

A thermal imaging–driven diagnostic framework was designed incorporating robust image preprocessing, multi-domain handcrafted feature extraction, and a hybrid feature selection strategy that combines the Coati Optimization Algorithm and the Marine Predators Algorithm. Customized deep learning models, including multilayer perceptron (MLP), recurrent neural network (RNN), attention-based convolutional neural network (CNN), and transfer learning–based architectures, were trained and evaluated using simulated thermal images representing COVID-19, pneumonia, and healthy conditions. Model interpretability was enhanced using Gradient-weighted Class Activation Mapping (Grad-CAM).

Results

The optimized framework achieved high classification performance, with accuracies of 98.58% using a 70/30 train–test split and 99.57% using an 80/20 split. Grad-CAM visualizations consistently identified disease-relevant thermal regions that contributed to model predictions, supporting both diagnostic reliability and interpretability.Conclusion:The proposed low-cost thermal imaging and deep learning framework demonstrates strong potential as an accessible, radiation-free solution for automated screening and monitoring of respiratory diseases. The high diagnostic accuracy and interpretability indicate its suitability for large-scale, resource-constrained healthcare settings.

Background

Miconazole nitrate, a BCS Class II drug (< 3 µg/mL solubility, poor skin permeability), requires enhanced topical delivery systems.

Objective

Develop optimized transethosomal gel for superior skin penetration and antifungal efficacy against Candida albicans.

Methods

Cold method preparation, Central Composite Design (CCD) optimization (soy lecithin 2.5–3.5% w/v, ethanol 20–60% v/v; n = 9 formulations). Evaluated vesicle size, entrapment efficiency (EE), zeta potential, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR) spectroscopy. Carbopol 934 gel incorporation. Assessed In vitro release, ex vivo Franz permeation (cellophane MWCO 12–14 kDa, PBS pH 7.4, 32 °C, 400 rpm; samples: 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24 h), antifungal disc diffusion, In vivo irritation (Wistar rats, OECD 404), Confocal Laser Scanning Microscopy (CLSM; Rhodamine B λex 540/λem 630 nm) .

Results

Optimized F-3: EE 81.56%, vesicle size 360.15 nm (Table 3). Transethosomal gel showed 48.76% permeation vs. plain gel (p < 0.05), inhibition zone 13.50 ± 0.02 mm vs. Micogel^® 9.60 mm, dermis penetration via CLSM.

Conclusion

CCD-optimized transethosomal gel enhances miconazole delivery vs. existing formulations, warranting clinical evaluation.

Graphical Abstract

Miconazole nitrate was formulated into transethosomes using the cold method with phospholipids, ethanol, and an edge activator to improve skin permeability. Formulation variables (ethanol and soy lecithin concentration) were optimized via Central Composite Design, with entrapment efficiency and vesicle size evaluated through 3D surface plots, and morphology confirmed by TEM. In vitro testing included antifungal activity against Candida albicans (disc diffusion) and drug permeation studies using a Franz diffusion cell. In vivo skin irritation tests were conducted on Wistar rats, while ex vivo penetration was assessed by CLSM using fluorescently labeled gel. The optimized formulation achieved high entrapment efficiency (~ 81.56%), small vesicle size (~ 360.15 nm), and stability, showing a larger inhibition zone than marketed cream, higher 24-hour cumulative drug release, minimal skin irritation, and confirmed deep skin penetration into the epidermis and dermis.

Abstract

The United States Food and Drug Administration (USFDA) regulates and inspects pharmaceutical drug products for its current good manufacturing process (cGMP) and data governance. The Food and Drug Administration (FDA) aims to monitor all drug substances intended for marketing within the United States to ensure compliance with its safety, efficacy, purity, and quality standards. An evaluation of Inspection trends and FDA FORM 483 observations for biologics from 2010 to 2025 reveals persistent areas of regulatory concern, evolving inspectional priorities, and significant disruptions due to global events like the COVID-19 pandemic.

Objective

The purpose of the study is to offer impartial insights into regulatory trends and to identify any underlying issues contributing to a site's non-compliance status. The trends in the inspection and issuance of FORM 483 for biologics for the past 15 years were analyzed to understand the probability of resulting enforcement actions. The study also aims to guide the biologic manufacturers and provide preventive measures to overcome possible regulatory violations.

Method

Cross-sectional examination of Inspection data and FORM 483 citations published in public databases by the FDA for inspections under the Biologics, covering the period from January 2010 to August 2025, was selected for the study. All the related metadata was accessed from the FDA Inspection Dashboard and Inspection Observation page on the FDA website. The data was deeply analysed, tabulated and understood the Code of Federal Regulations (CFR) violations and their root cause.

Results

The data collected was thoroughly evaluated, summarized, and the most common violations were identified. From the study, it is evident that the frequent violations are related to cGMP issues, like failure to follow written Standard Operating Procedures (SOP), failure to maintain contemporaneous documentation, and not performing thorough investigation before batch release, corresponding to 34%, 21%, and 14%, respectively.

Conclusion

The trend in the inspections and FORM 483 is mainly on cGMP Violations. A complete understanding of the FDA inspection and the requirements for good biologic manufacturing process is a must. Following proper Data governance principles and maintaining an internal audit checklist, training of employees on both evolving technology and guidelines will make an effective change and possibly reduce enforcement actions.

Background

Obesity, characterized by lipid accumulation, oxidative stress, and inflammation, remains a major public health challenge. This study aimed to investigate the therapeutic efficacy of diosgenin-loaded silver nanoparticles (Dio-AgNPs) in modulating obesity-induced metabolic and molecular dysfunction through integrated biochemical, gene expression, and molecular docking approaches.

Methods

Male albino rats were randomly assigned to control and experimental groups, with Dio-AgNPs administered at two distinct doses. Dio-AgNPs were synthesized and characterized using UV-Vis spectroscopy, TEM, DLS, and zeta potential measurements to confirm particle size and stability. Biochemical analyses included serum lipid profile (triglycerides, total cholesterol, LDL-c, HDL-c), fasting glucose, insulin levels, and HOMA-IR for insulin sensitivity. Oxidative stress markers (MDA) and antioxidant enzymes (SOD, CAT, GPx) were measured spectrophotometrically. Inflammatory cytokines (TNF-α and IL-6) were quantified by ELISA. Gene expression of lipogenic enzymes (ACC and FAS) and antioxidant-related genes was assessed using quantitative real-time PCR (qRT-PCR). Molecular docking simulations were performed to evaluate diosgenin’s binding affinities and interactions with ACC and FAS enzyme active sites.

Results

Dio-AgNP-treated rats showed significant reductions in serum triglycerides, total cholesterol, LDL-c, and fasting glucose compared to controls, while HDL-c and insulin sensitivity were markedly improved. Antioxidant enzyme activities (SOD, CAT, GPx) increased significantly, and MDA levels decreased, indicating oxidative stress attenuation. ELISA confirmed reduced levels of TNF-α and IL-6, revealing anti-inflammatory effects. Gene expression analysis demonstrated dose-dependent downregulation of ACC and FAS, along with upregulation of antioxidant and insulin-responsive genes. Molecular docking results revealed strong binding interactions of diosgenin with both ACC and FAS enzymes, supporting enzymatic inhibition and the transcriptional trends observed. Silver nanoparticle delivery enhanced bioavailability and target specificity.

Conclusion

This is the first report, to our knowledge, that combines biochemical, gene expression, and molecular docking data to investigate Dio-AgNPs’ anti-obesity effects. The findings highlight a promising nanomedicine-based approach for metabolic regulation and pave the way for further research in therapeutic nanoparticle design and application.