Journal of Pharmaceutical Innovation最新文献

Background

Zinc oxide nanoparticles (ZnO-NPs) are versatile metal oxide nanomaterials with unique physical and chemical properties, yet their synthesis often lacks systematic optimization. The biomedical potential of colchicine-loaded ZnO-NPs (C-ZnO-NPs) also remains underexplored.

Methods

This study utilized the Box-Behnken Design (BBD) to optimize the synthesis of C-ZnO-NPs using zinc acetate dihydrate (ZnA) molarity (0.25–1 M), stirring speed (500–1000 rpm), and temperature (60–90 °C) as variables.

Results

The optimized formulation (F18) exhibited an average particle size of 390.8 ± 71.8 nm, a zeta potential of − 15.52 ± 0.42 mV, and entrapment efficiency of 80.22 ± 5.54%. UV–Vis spectroscopy showed absorption peaks at 247 and 357 nm, corresponding to COL and ZnO-NPs, respectively. Energy-dispersive X-ray (EDX) spectra indicated Zn, O, and notable carbon signals, while X-ray diffraction (XRD) confirmed crystalline ZnO. In silico docking demonstrated strong binding affinities of ZnO-NPs with peptide deformylase (PDF) receptors from Staphylococcus aureus (S. aureus) (PDB ID: 3U7L) and drug-resistant S. aureus (PDB ID: 6JFS), supporting their potential antibacterial activity. In vitro testing showed concentration-dependent inhibition of S. aureus, although no additional contribution from COL could be confirmed under the tested conditions.

Conclusion

Although these findings highlight the antibacterial potential of ZnO-NPs, comprehensive evaluation through cytotoxicity, hemolysis, endotoxin, and biorelevant release studies is essential before considering their suitability for biomedical applications.

The current study was aimed to develop and optimize a propellant-free, herbal rutin-loaded film-forming spray (FFS) for wound healing, utilizing a chitosan–polyvinyl alcohol (PVA) polymeric matrix. Rutin was solubilized in ethanol and incorporated into a polymeric solution of chitosan and PVA, with propylene glycol serving as a plasticizer and permeation enhancer. A Central Composite Design (CCD) was employed to optimize the formulation. The resulting film forming spray was characterized for various physicochemical properties such as viscosity, drug release, spray angle, breaking strength, average weight per dose, biodegradability study and in vivo study in rats using excision wound model. The FFS demonstrated physicochemical characteristics, including rapid drying, uniform spray pattern, and appropriate viscosity 14.7 cp. and immediate drug release 97% for topical application. The spray angle at 70 ± 3° provided a broad surface coverage when sprayed at a distance of 14–15 cm, suitable for covering 201 ± 11 cm² wound area. In vivo wound healing in Wistar rats conducted over 21 days, showed 99.74% contraction with the test versus 97.88% and 65.55% in the standard and control groups, respectively. Thus, significantly accelerated wound contraction was observed in the test group as compared to both standard and control. The propellant-free rutin-loaded FFS offers a patient-friendly, effective alternative for topical wound care, demonstrating significant potential in promoting wound healing.

Graphical Abstract

Conventional dressings cannot self-repair when ruptured during movement, reducing their lifespan and therapeutic benefits. Moreover, it is unable to provide an ideal environment for patients with diabetes due to poor angiogenesis, excessive oxidative stress, and prolonged inflammation. We prepared a self-healing and on-demand removable hydrogel film composed of fenugreek gum (FG), which possesses anti-inflammatory and antioxidant properties. FG was extracted from fenugreek seeds, and hydrogel films were prepared using the solvent casting method with borax as a cross-linker. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were performed to evaluate cross-linking and surface morphology. The hydrogel films were further characterized for tensile strength, wound absorption capacity, rheological behavior, water vapor transmission rate (WVTR), self-healing efficiency, and antioxidant capacity. The total phenolic and saponin content of FG was measured at 68.16 mg gallic acid equivalents (GAE)/g and 131.53 mg diosgenin equivalents (DE)/g, respectively. The 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH) scavenging activity of 90.52% was observed at 10 mg/ml. The gum showed good anti-inflammatory activity with a maximum inhibition of 64.79 ± 2.13% at 1000 µg/mL. FTIR confirmed the cross-linking between borax and FG. The surface morphology of the cross-linked hydrogel film exhibited smaller pores with a greater cross-link density, as revealed by SEM. The optimized cross-linked hydrogel film demonstrated self-healing capabilities with a healing efficiency of 97.36 ± 0.62%. Furthermore, it enables complete detachment from the wound surface through glucose-induced dissolution, which may limit subsequent scarring caused by stripping of wound dressings. The best hydrogel film exhibited properties including thickness (0.175 mm), WVTR (1071.95 g/m²/day), Tensile strength (13.3 N/mm² dry; 10.95 N/mm² wet), fluid absorption capacity (555.2%), DPPH scavenging activity (55.16%), and on-demand removal capability in response to glucose. Therefore, this versatile fenugreek-gum based hydrogel film may provide a new paradigm for designing on-demand removable wound dressing biomaterials for managing diabetic wounds.

Graphical Abstract

Background

Prefilled syringes are commonly used in pharmaceutical products; however, volatile organic compounds leaching from plastic or elastomeric components can pose potential health risks. A sensitive and specific GC-FID method was developed and validated for the determination of volatile organic compounds in Sumatriptan Injection (6 mg/0.5 mL).

Methodology

The method targets a mixture of volatile organic compounds with boiling points ranging from 40 °C to 225 °C. Separation was achieved using an HP-5-MS column, with a temperature program of 10 °C/min for the first 10 min and 25 °C/min thereafter. Nitrogen was used as the carrier gas (25 mL/min), with hydrogen (30 mL/min) and zero air (300 mL/min) for flame generation.

Results

The method demonstrated high linearity (r²> 0.99), with a limit of quantification of 0.060 ppm. The Limit of Quantification accuracy and precision ranged from 77.83% to 115.55% and ≤ 4.88% RSD, respectively. Accuracy at 50%, 100%, and 150% concentration levels ranged from 94.26–105.21%, 93.78–97.68%, and 89.56–94.49%, respectively, while precision (%RSD) at these levels ranged from 1.98–2.65%, 1.75–2.32%, and 0.16–0.50%, respectively.

Conclusions

The validated GC-FID method is accurate, precise and highly sensitive for detecting trace-level VOCs in parenteral formulations. With excellent linearity and reproducibility, it is well-suited for risk assessment and ensuring the quality and safety of injectable drug products such as Sumatriptan Injection.

Polo-like kinase 1 (PLK1) is a serine/threonine kinase critically involved in mitotic progression and is frequently overexpressed in breast cancer, making it an attractive therapeutic target. An integrated in silico approach combining molecular docking, activity prediction, molecular dynamics (MD) simulation, and Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) calculations was employed to identify potential PLK1 inhibitors. An initial library of 59 drug-like phytochemicals from Clausena anisata was screened against the kinase domain of PLK1, yielding 13 hits (docking ΔG ≤ − 8.6 kcal/mol), all of which interacted with key hinge and pocket residues, including Cys133, Leu59, and Phe183. All hits were predicted to exhibit apoptotic and antineoplastic properties with a probability of active (Pa) value > 0.3 and sub-micromolar to low-nanomolar IC₅₀ values. MD simulation revealed that the top 6 lead compounds exhibited the most favorable dynamic stability and compactness. MM-PBSA binding free energies ranked CID 5315947 (–96.1 ± 16 kJ/mol), CID 10448976 (–95.8 ± 9.5 kJ/mol), and CID 6439823 (–94.9 ± 14.2 kJ/mol) as the strongest binders, driven predominantly by van der Waals interactions. Per-residue energy decomposition revealed that Glu69 is a novel critical modulator of selectivity and kinase inactivation. Collectively, our multi-tiered computational approach identifies promising natural scaffolds for PLK1 inhibition and provides a robust framework for lead optimization in breast cancer therapy.

Graphical Abstract

Objective

To develop and optimize tapinarof-loaded proniosome gel for enhanced topical therapy for plaque psoriasis.

Methods

Tapinarof-loaded proniosomes were prepared via the coacervation phase separation method and optimized via the Box–Behnken design, with the surfactant concentration (Span 60: 900–1800 mg), membrane stabilizer content (cholesterol: 200–300 mg), and phospholipid amount (soyubicin: 800–900 mg) as independent variables. The optimized proniosomal formulation was incorporated into different gel bases (Carbopol 934, HPMC K15M, their combination, and sodium alginate). The physicochemical properties, ex vivo permeation, stability, and in vivo antipsoriatic efficacy of the formulations were characterized in an imiquimod-induced psoriasis model.

Results

The optimized proniosomal formulation (Span 60: 1350 mg, cholesterol: 250 mg, soya lecithin: 850 mg) exhibited excellent entrapment efficiency (90.93%), drug release (96.98%), and vesicle size (118.56 nm) with minimal prediction error (0.066–2.166%). Among the gel formulations, NG3 (Carbopol 934-HPMC K15M combination) demonstrated superior properties, with an optimal pH (6.53), spreadability (15.74 g·cm/sec), and drug content (97.92%). Ex vivo studies revealed significantly greater steady-state fluxes (28.37 µg/cm²/h) and permeability coefficients (5.67 × 10⁻³ cm/h) for NG3 than for the other formulations. The formulation-maintained stability under accelerated conditions, with a statistically insignificant 5.9% reduction in drug content after 3 months (p > 0.05). Compared with the marketed formulation, NG3 had significantly greater antipsoriatic efficacy in vivo, with lower PASI scores (1.75 vs. 2.86), reduced skin thickness (0.89 mm vs. 1.14 mm), and decreased inflammatory cytokine levels (TNF-α: 36.25 vs. 54.37 pg/mg).

Conclusion

The developed proniosomal gel significantly enhances the therapeutic efficacy of tapinarof for plaque psoriasis treatment through improved skin penetration and targeted delivery, offering potential for reduced application frequency and enhanced patient compliance in clinical settings.

Graphical Abstract

Background

Carvedilol (CAR) is a non-selective beta-blocker used in treating hypertension and heart failure. Existing analytical methods for CAR quantification face challenges in sensitivity, environmental sustainability, and efficiency.

Objectives

This study aimed to develop an innovative, highly sensitive, and environmentally friendly analytical method for picoscale determination of CAR in pharmaceutical formulations and biological samples.

Method

The research utilized a microwave-assisted micro-level Mannich-type derivatization to generate a CAR-linked fluorescent biosensing probe on TLC plates. The method development integrated principles of white analytical chemistry and Quality by Design (QbD) to optimize performance and minimize environmental impact.

Results

The developed method demonstrated exceptional sensitivity with detection and quantification limits in the picogram range (LOD: 3.0 pg/band, LOQ: 10 pg/band), surpassing conventional techniques. It showed high accuracy and precision in both pharmaceutical formulations (99.69-100.55% recovery) and biological samples (91.42–96.50% recovery in human plasma). The method generated zero organic waste and consumed minimal resources, achieving higher scores on analytical profile tools compared to conventional methods.

Conclusion

This research presents a significant advancement in CAR analysis, offering a highly sensitive, eco-friendly, and efficient analytical tool that balances analytical performance with environmental responsibility and user-friendliness, addressing key limitations of traditional analytical approaches.

Purpose

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer and has poor survival rates despite decades of therapeutic advances. Small-molecule tyrosine kinase inhibitors, such as erlotinib (ERL), are widely used for the treatment of primary lung tumors. However, oral administration, the predominant route, often results in suboptimal drug concentrations at the tumor site and dose-limiting systemic toxicities. The objective of this study was to improve the pharmaceutical properties of ERL by developing an inhalable polymeric micellar formulation for targeted pulmonary delivery.

Methods

A co-solvent evaporation method was employed to develop a micellar formulation of ERL composed of TPGS-b-PCL copolymers. The optimal formulation was characterized by high-performance liquid chromatography, dynamic light scattering, and transmission electron microscopy. The in vitro drug release and aerosol performance, through NGI, were evaluated. In vitro cytotoxicity using MTT and apoptosis assays was performed to assess the anticancer efficacy against A549 cells.

Results

The optimal ERL-loaded micelles (TPGS-b-PCL) exhibited a spherical shape with a mean diameter of ~ 44 nm, high encapsulation efficiency (~ 90%), and a slightly positively charged zeta potential. ERL was released relatively slowly from the copolymers, and aerosol performance testing demonstrated favorable aerosol properties, with a mass median aerodynamic diameter < 3 μm and a fine particle fraction (FPF_< 5) > 80%. The feasibility study using cytotoxicity assays showed that ERL-loaded micelles achieved potent antitumor activity.

Conclusion

These findings highlight the potential of ERL-loaded TPGS-b-PCL for local treatment of NSCLC. Further investigation is necessary to assess the tolerability and efficacy of the inhalable ERL micellar therapy in vivo using appropriate preclinical NSCLC models.

Diabetes mellitus is a chronic metabolic disease associated with progressive organ damage driven by hyperglycaemia-induced oxidative stress, inflammation, and cellular dysfunction. Cardiovascular complications remain a major cause of morbidity and mortality in diabetic patients. This study evaluated the antidiabetic, hepatoprotective, and pancreatic protective effects of a polyherbal formulation (PHF) comprising Curcuma longa, Nigella sativa, Prunus mahaleb, and Vitis vinifera in streptozotocin (STZ)-induced diabetic rats, integrating network pharmacology analysis with experimental validation. Network pharmacology analysis was performed to identify potential PHF-related targets and pathways associated with diabetes-related tissue injury. Rats were assigned to control, diabetic, metformin-treated, and PHF-treated (500 and 1000 mg/kg) groups. The 500 mg/kg dose was selected as an intermediate dose based on prior experimental studies reporting its biological relevance and safety in plant-derived formulations. Blood glucose, serum insulin, lipid profile, and pancreatic enzymes were measured. Hepatic and pancreatic tissues were examined using hematoxylin and eosin (H&E), Masson’s trichrome (MT), periodic acid–Schiff (PAS) staining, and immunohistochemistry for endothelial nitric oxide synthase (eNOS), B-cell lymphoma 2 (Bcl-2), Bcl-2–associated X protein (Bax), caspase-3, tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and vascular endothelial growth factor (VEGF). PHF treatment, particularly at 1000 mg/kg, normalised blood glucose (p < 0.001), improved serum insulin, corrected dyslipidaemia, and restored amylase and lipase levels. Histological analysis demonstrated attenuation of steatosis, necrosis, fibrosis, and pancreatic β-cell loss. Immunohistochemical analysis showed reduced Bax and caspase-3 protein immunoreactivity and increased Bcl-2 and VEGF protein expression in PHF-treated groups. Network pharmacology analysis revealed 333 shared targets between PHF and diabetes-related injury, enriched in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), advanced glycation end product–receptor for AGE (AGE–RAGE), TNF, and metabolic signalling pathways. Hub genes including AKT1, IL6, TNF, STAT3, PTGS2, CASP3, and BCL2 showed reciprocal consistency between network pharmacology predictions and experimental immunohistochemical observations. To sum up, these findings support the potential of PHF as a multi-target therapeutic strategy against diabetes-induced hepatic and pancreatic injury.

The pharmaceutical manufacturing industry faces critical challenges in maintaining consistent quality control during high-speed tablet production, where existing tracking methods suffer from identity switches, temporal inconsistencies, and inaccurate counting mechanisms. This paper presents the Multi-Scale Pharmaceutical Defect Tracker with Adaptive Confidence and Counting (MS-PDTAC), a comprehensive real-time system for defect detection, tracking, and counting in pharmaceutical tablet production lines. The system employs a dual-stream concurrent processing architecture integrating YOLOv8-based object detection with sophisticated tracking mechanisms and self-supervised learning capabilities. The primary processing pipeline implements multi-stage false detection filtering through geometric validation, non-maximum suppression, and temporal consistency checking, followed by multi-scale histogram feature extraction at four resolution levels to capture defect characteristics across varying scales. Detection-to-track association employs Hungarian algorithm optimization with composite cost matrices that integrate spatial distance, appearance similarity, and confidence quality components, enhanced by a spatio-temporal attention mechanism that dynamically weights these factors based on trajectory prediction, temporal consistency, and feature matching reliability. State estimation utilizes Kalman filtering for position prediction and exponential smoothing for feature refinement, while defect state lifecycle management implements tentative-to-active state transitions, ensuring only validated defects contribute to final counts. Multi-method line crossing detection combines direct position monitoring, trajectory history analysis, and area-based detection to achieve robust counting accuracy. A concurrent self-supervised learning stream continuously adapts confidence thresholds and feature weights through statistical feedback mechanisms operating every 50 frames, enabling real-time system optimization without manual intervention. Comprehensive evaluation on custom pharmaceutical datasets demonstrates perfect counting accuracy (100%) with zero absolute count error across all seven defect categories (black dots, broken tablets, color mismatches, cracks, dual caps, empty capsules, and foreign particles), significantly outperforming the base methodology that suffers from over-counting, false positives, and identity switching issues.