Journal of Pharmaceutical Innovation最新文献

Purpose

This study aims to identify suitable protectants for the freeze-drying of functional peptide-assembled polymer nanoparticles (AsNPs) and polymer nanoparticles (PNPs) composed of methoxy poly(ethylene glycol)-ε-poly(caprolactone) (mPEG-PCL), based on their physicochemical properties and redispersibility after freeze-drying.

Methods

Nanoparticle suspensions containing various protectants were freeze-dried using a standard freeze dryer. The average hydrodynamic diameter (mean particle size), zeta potential, and polydispersity index of AsNPs and PNPs were measured using dynamic light scattering before and after freeze-drying. Furthermore, the effect of freeze-drying on the oligonucleotide-loading capacity of AsNPs was examined.

Results

Hydroxypropyl-β-cyclodextrin (HP-β-CD) was identified as an effective protectant for freeze-drying AsNPs and PNPs composed of mPEG (5 kDa)-PCL (10 kDa). HP-β-CD likely interacts with the polyethylene glycol (PEG) chains of PNPs, preventing aggregation by reducing particle contact during redispersion. The oligonucleotide loading efficiency of AsNPs with a nitrogen-to-phosphate (N/P) ratio of 10 or higher remained comparable to that before freeze-drying.

Conclusion

HP-β-CD is a promising protectant for the freeze-drying of AsNPs, effectively minimizing nanoparticle aggregation caused by handling or hydrolysis. Therefore, AsNP formulations incorporating HP-β-CD show potential as practical drug delivery system carriers for nucleic acid-based pharmaceuticals.

Graphical Abstract

Purpose

cute wounds are driven by persistent oxidative stress and impaired tissue regeneration. Glutathione (GLU), a key antioxidant, offers therapeutic potential but faces instability and poor dermal penetration.

Methods

A nanogel delivery system combining GLU–acacia complex in an alginate matrix was developed using ionic gelation. Physicochemical properties, in vitro release, and long-term stability were assessed. Wistar rats with full-thickness wounds were treated for 14 days, and healing biomarkers were quantified. 

Results

The nanogel exhibited 99.6 nm particle size, −33.0 mV zeta potential, 91.6% entrapment efficiency, and sustained GLU release (87% at 24h). Wound closure reached 94.3%, significantly outperforming controls (p < 0.001). VEGF, TGF-β1, and collagen I were upregulated; IL-6 showed controlled elevation. 

Conclusion

The novel glutathione–acacia–alginate nanogel with redox-modulating properties offers a stable, redox-active system that enhances wound healing via sustained antioxidant delivery and biomarker-guided regeneration. 

Graphical Abstract

This graphical abstract illustrates the development and therapeutic mechanism of a redox-modulating nanogel designed for acute wound healing. The formulation involves the complexation of glutathione (GLU) with acacia (ACC), enhancing its redox stability and loading capacity. This GLU–ACC complex is encapsulated within a sodium alginate (SA) matrix, forming a biocompatible nanogel suitable for dermal application.

Upon topical application to a acute wound, the nanogel facilitates targeted antioxidant delivery, promoting tissue regeneration. The therapeutic cascade includes a significant upregulation of VEGF and TGF-β₁, markers of angiogenesis and tissue remodelling, alongside an increase in IL-6, indicating an acute phase response. These biomolecular effects contribute to accelerated wound closure and enhanced healing outcomes.

The illustration highlights the nanogel’s multi-level action; from molecular stabilisation and encapsulation to biomarker modulation at the wound site, supporting its potential as an advanced platform for oxidative wound management.

Purpose

The aim of the present study was to develop nanoparticles of acyclovir using chitosan as a natural polysaccharide for improving its poor oral bioavailability, dosing frequency and to reduce side effects and to assess the pharmacokinetic profile using PK-Sim software.

Methods

The ionic gelation method was used to synthesize acyclovir loaded chitosan nanoparticles using STPP (sodium tripolyphosphate) as crosslinking agent. For formulations (F1-F9), a constant ratio of polymer (chitosan) and crosslinking agent (STPP) was maintained. The prepared formulations were characterized by determining particle size using DLS, surface morphology using SEM, percentage of yield, entrapment efficiency, drug- excipient compatibility by Fourier transform infrared Spectroscopy(FT-IR), in-vitro release study and in-silico study using PK- Sim software.

Results

The particle size of prepared nanoparticles were reported to be within 100 nm with a moderate polydispersity index. The SEM study indicated oval shape with microscopic pores. Higher encapsulation efficiency (⁓98%) demonstrated the potential of chitosan as a drug carrier. FT-IR study has confirmed the compatibility between acyclovir and other excipients. The prepared F3 formulation showed 23.8% drug release over 3 h indicating a slow release of acyclovir that may reduce dosing frequency and improve patient compliance. The drug release was found to follow Korsemeyer-Peppas kinetics with diffusion-controlled release of acyclovir. Additionally, in-silico study predicted improved plasma profile compared to the conventional oral dosage form.

Conclusion

The study findings suggested F3 as the optimized formulation with controlled release ability of incorporated drug, acyclovir and potential of reducing dosing frequency while minimizing side effects.

Graphical Abstract

Cystic fibrosis (CF) is a genetic disorder characterized by thick mucus accumulation in the lungs, leading to chronic infections and inflammation. Ivacaftor, a CFTR potentiator, requires frequent dosing in its conventional form, reducing patient compliance. This study aims to develop ivacaftor-loaded nanoparticles for pulmonary drug delivery using poly(lactic acid) (PLA) and chitosan. Preformulation studies, such as solubility and melting point, as well as drug-excipient compatibility (FTIR, XRD, DSC), were performed. Nanoparticles were formulated via solvent evaporation and ionic gelation, followed by PEG surface modification for enhanced stability. A Plackett-Burman design was used to screen key formulation variables. First, a suite of ivacaftor-loaded nanoparticles were prepared using different formulation parameters to study the effects of these parameters on size, drug loading, encapsulation efficiency, and morphology (SEM). In-vitro release profiles were also conducted along with an In-vitro lung deposition study using a cascade impactor. Further optimization using a three-level factorial design yielded optimized batches. Prepared nanoparticles were spherical with size ranging from 110 to 763 nm for PLA nanoparticles and 149 –1165 nm for chitosan nanoparticles, respectively. The percentage encapsulation efficiency (%EE) of 80.96–91.5% for PLA nanoparticles and 63.14–91.42% for chitosan nanoparticles. Optimized formulations achieved particle sizes below 300 nm, good entrapment efficacy of 89.44%, drug loading from 3 to 5.6%, and lower PDI values enabling deeper lung penetration. In vitro studies demonstrated sustained drug release for 24 h (chitosan) and 36 h (PLA), significantly reducing dosing frequency compared to marketed ivacaftor tablets (Kalydeco 150 mg), which require administration 2–3 times daily. The freeze-dried NPs Powder of PLA and Chitosan showed the required mass median aerodynamic diameter of 5.39 μm and 4.75 μm, respectively, and greater fine particle fraction (39.4965% and 24.9471% ). These findings underscore the potential of ivacaftor-loaded nanoparticles as an effective pulmonary delivery system, prolonging drug release and improving patient adherence for CF management.

Purpose

Bisphenol A (BPA) is a widely used industrial chemical that can induce oxidative stress, hematotoxicity, and neurotoxicity via mitochondrial dysfunction and apoptosis. This study evaluated whether boric acid (BA) mitigates BPA-induced systemic injury in male Wistar rats using integrated in vivo and network analyses.

Methods

Forty-two rats were assigned to six groups and treated for 28 days with BPA (130 mg/kg/day, oral), BA (100 or 200 mg/kg/day, i.p.), or combinations.

Results

BPA markedly increased total oxidant status (TOS) and oxidative stress index (OSI) and reduced total antioxidant status (TAS), indicating severe redox imbalance. BPA also decreased RBC, PLT, Hb, Hct, and bone marrow nucleated cells, consistent with myelosuppression. In brain tissue, BPA increased Bax, caspase-3, and cytochrome c immunoreactivity while decreasing Bcl-2, accompanied by neuronal degeneration and necrosis. BA co-treatment improved TAS, reduced OSI, restored hematological indices and BMNC counts, and attenuated pro-apoptotic signalling in a dose-dependent manner, with BA (200 mg/kg) showing the strongest protection. Network pharmacology highlighted BPA-associated neuroactive ligand–receptor interactions and BA-associated antioxidant and DNA repair modules, with enrichment of oxidative stress response, apoptotic regulation, and DNA damage repair pathways.

Conclusion

Collectively, BA reduced BPA-induced oxidative stress, hematological suppression, and neuronal apoptosis in rats, supporting its protective potential as a redox-modulating adjunct in BPA exposure models.

Real-time monitoring of particle size distribution (PSD) is a promising tool for the robust control of wet fluidized bed granulation processes, where rapid particle growth and moisture fluctuations limit the applicability of conventional offline analyses. Although real-time laser diffraction (RT-LD) with closed-loop continuous sampling (CLC) is widely used as a Process Analytical Technology (PAT) tool, continuous sampling can introduce process disturbance, contamination risks, and operational constraints, particularly under wet granulation conditions. This Research Letter reports a novel, flexible, and cost-effective RT-LD approach incorporating a micro-sampling probe that utilizes a portable closure mechanism to enable intermittent, low-volume sampling while maintaining stable airflow conditions. The system was evaluated during wet fluidized bed granulation using a model process and directly compared with conventional CLC sampling. The temporal evolution of Dv10, Dv50, and Dv90 measured by the micro-sampling system closely matched those obtained using CLC, demonstrating equivalent particle size tracking throughout granulation. By minimizing sample residence time and reducing sampling-induced artifacts, this flexible RT-LD approach provides a practical solution for real-time PSD monitoring with cross-granulator portability, offering a cost-effective strategy for PAT implementation from development to manufacturing.

Background

4D printing, an advanced evolution of additive manufacturing that incorporates time-dependent structural transformation, is gaining prominence as a powerful platform for designing responsive drug delivery systems. In oral therapeutics, a major challenge is achieving prolonged gastric retention to improve the bioavailability of drugs with narrow absorption windows or that are unstable in the intestinal milieu. Addressing this limitation, recent studies and technological advances have focused on 4D-printed systems capable of programmed morphological adaptation for controlled gastric retention.

Purpose

This review systematically evaluates recent patent filings on shape-transformable 4D-printed drug delivery devices for gastric applications.

Methods

It analyzes the current intellectual property landscape, emphasizing the diverse engineering strategies, polymer selections, and stimuli-responsive mechanisms proposed to create systems that unfold, expand, or transform in response to gastric conditions.

Results

The patents highlight innovative approaches that encompass bilayer constructs, stimuli-sensitive smart materials, and bioinspired configurations, such as origami and moisture-actuated designs. This review focuses on patented developments, capturing emerging technological directions and key trends that shape the 4D-printed gastric drug delivery domain. This approach provides insight into traditional design strategies, emerging technological trends, and commercialization-oriented innovations.

Conclusion

Additionally, it discusses ongoing challenges and prospective opportunities, encouraging interdisciplinary collaboration to overcome material, manufacturing, and regulatory hurdles. Overall, the review highlights the unique suitability of 4D printing for gastrointestinal applications, where intrinsic physiological triggers, such as pH, temperature, and gastric fluid, can be leveraged to achieve programmable, adaptive, and controlled drug delivery. As the field evolves, these patented innovations are expected to drive advancements toward personalized and precisely controlled oral drug delivery systems.

Despite the recent pharmaceutical advancements and dosage form modifications, the poor dissolution rates of BCS class II drugs remains a significant challenge. The aim of this study was the development of centrifugally spun drug loaded microfibers with improved dissolution rate with focus on optimizing the process variables. Drug loaded microfibers were prepared by centrifugal melt spinning (CMS) with optimized process variables (2450 rpm, longitudinal pore shaped spinneret, 50 cm spinneret-collector distance) using a mixture of sucrose, drug and a hydrophilic polymer, hydroxypropyl cellulose (HPC). Microfibers were characterized by using SEM, DSC, XRD and FTIR spectroscopy. Microfibers demonstrated production yield of 45 ± 4% with average diameter of 15 ± 5 μm and disintegration time of 8 ± 2 s. In-vitro dissolution of flurbiprofen from microfibers showed > 85% release of drug within two minutes which was ∼60% more than drug alone. PXRD, DSC analysis has shown a change in crystalline nature of drug in microfibers and FTIR showed an interaction of flurbiprofen with hydrophilic excipients of formulation. This study concludes that flurbiprofen loaded microfibers showed rapid in-vitro dissolution of drug and centrifugal melt spinning is a promising approach for the production of quick release formulation of poorly soluble drug.

The purpose of current study was to develop a sensitive, rapid, cost-effective, and precise Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for the simultaneous estimation of asiaticoside and chlorhexidine by using an analytical quality-by-design approach. Initially, important analytical quality-by-design prerequisites such as analytical target profile and critical analytical attributes, like area and tailing factor, were defined. The final selected chromatographic condition for the analysis of asiaticoside and chlorhexidine consists of a stationary phase {COSMOSIL 5C18-MS-II; 250 mm × 4.6 mm i.d, 5 μm}, and the Mobile phase was S_mix (Acetonitrile: Methanol (20:20) and orthophosphoric acid (2.5 mM; pH 3.5) in the ratio of (40:60) at a flow rate of 1.0 mL/min. The diversity of Critical Analytical Attributes with different inputs was explained using an Ishikawa fishbone diagram. The Taguchi design was selected as the first screening design to choose the critical material attributes that influence the method development. Subsequently, for more systemic optimization of the chromatographic techniques and evaluation of Critical Analytical Attributes, central composite design was employed. The developed method validation performed in accordance with ICH Q2(R2) guidelines confirmed excellent linearity (R² ≥ 0.999), accuracy (99.21–101.15%), intra- and inter-day precision (%RSD ≤ 2%), specificity, and robustness against deliberate variations. The method was successfully applied to asiaticoside-chlorhexidine-loaded nanostructured lipid carriers’ formulations, demonstrating high entrapment efficiency, asiaticoside (87%) and chlorhexidine (84%), with a sustained biphasic release profile of ~ 75% drug release over 24 h, contrasting with the rapid release of pure drugs. This analytical quality-by-design-driven approach not only ensures scientific reliability but also regulatory compliance, offering a precise, accurate, and quality-assured analytical tool for the simultaneous estimation of asiaticoside and chlorhexidine in advanced wound-healing systems.

Graphical Abstract

Purpose

Hydrogels are three-dimensional, crosslinked polymeric systems with high hydrophilicity and biocompatibility, making them ideal materials for wound healing applications. In this study, a silver nanoparticle (AgNP)-loaded chitosan–poly (vinyl alcohol) (CS–PVA) hydrogel was developed using a novel, simple, and cost-effective approach. In this approach, sodium borohydride (NaBH₄) simultaneously acts as a reducing agent for AgNP synthesis and as a physical crosslinking agent for hydrogel formation.

Methods

AgNPs were synthesized via NaBH₄-mediated reduction and characterized by dynamic light scattering and UV–Vis spectroscopy. The resulting hydrogels were evaluated by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray (EDS) spectroscopy, swelling, porosity and mechanical test. In vitro biocompatibility and wound healing potential were assessed using cell viability assays and a scratch wound assay.

Results

Among all formulations, M30, an AgNP-loaded CS–PVA hydrogel, prepared with medium molecular weight (MMW) chitosan and 30 mL of AgNP suspension, had the best overall performance with the highest swelling degree, favorable mechanical performance. It maintained cell viability above 80% at 24 and 48 h, and showed the greatest wound closure rate, even at low AgNP concentration.

Conclusion

The results demonstrate that AgNP-loaded CS–PVA hydrogels prepared using NaBH₄ as a dual-function agent exhibit promising biocompatibility and wound healing potential even at low AgNP content. To the best of our knowledge, this study is the first to demonstrate the dual functionality of NaBH₄ in a single-step approach as both a reducing and physical crosslinking agent, providing a simple and promising strategy for the development of next-generation wound dressing materials without need for additional chemical crosslinkers.