Recent Advances in Drug Delivery and Formulation - Online First

Norfloxacin (NFX) is a wide-spectrum antibacterial agent that suffers from low water solubility and first-pass metabolism. This diminishes its oral bioavailability by 60-70%.

This work aims to formulate a topical gel of NFX-loaded lipid polymer hybrid nanoparticles (NFX-LPHNPs) that combine the merits of liposomes and polymeric nanoparticles to overcome these problems.

NFX-LPHNPs formulations were developed using Precirol ATO (lipid) and Eudragit RL100 (polymer). They were characterized for particle size, uniformity of distribution, entrapment efficiency, zeta potential, and in-vitro release. Box–Behnken design was applied to study sequentially different variables' impact on material attributes. Then the optimized formula was re-evaluated, and incorporated in an HPMC-gel formulation. The gel formulation was evaluated for its physical properties, in vitro-release, and antibacterial activity.

NFX-LPHNPs exhibited particle sizes ranging from 28.92 to 730.30 nm. Particles were uniformly distributed with a positively charged surface (indicated by zeta potential with values from +3.91 to +60.2 mV). Formulations showed a % cumulative drug release of 87.9-100% in 8 h. The optimized formula showed a satisfied fit of measured-to-predicted responses with 159 nm particle size, 92.61% release and 79.2% entrapment efficiency. Gel formulation showed a sustained release over 24 h. Antibacterial testing against Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa revealed enhanced activity of NFX-LPHNPs against these pathogens compared to bare NFX loaded gel.

These results illustrated the high potential of lipid-polymer hybrid nanoparticles to improve NFX activity against resistant pathogens common in burn infections. Moreover, the topical application helps overcome Norfloxacin oral-associated problems.

Healing full-thickness wounds is often challenging and time-consuming, with complications such as scarring and infections. The standard treatment, split skin grafting, has limitations due to the availability of healthy donors and suitability for immunocompromised patients.

Autologous platelet lysate (PL) has been popular for tissue regenerative potential because it contains growth factors (GF) and is a safer option for bedridden patients with weak immune systems. However, PL has inconsistent clinical efficacy, high costs, and a short half-life. To address these issues, this study explores a novel delivery system by fabricating a chitosan/nanocrystalline cellulose (CS/NCC) hydrogel to sustainably deliver autologous PL to the wound site. Notably, NCC was prepared from kenaf bast fibers using acid hydrolysis and integrated into the CS matrix through physical entrapment without any chemical crosslinkers. The composite hydrogel was then enriched with autologous PL and further characterized for its physicochemical properties, in vitro GF release, and compatibility with skin cells. At the molecular level, gene expression of wound healing genes was facilitated using qPCR, revealing that the PL-supplemented hydrogel upregulated the expression of extracellular matrix genes. An in vivo study using a full-thickness wound model demonstrated that the CS-NCC-PL hydrogel dressing achieved 81.8% wound closure within 14 days, compared to the control groups.

Histological analysis indicated enhanced re-epithelialization, angiogenesis, and collagen deposition. Particularly, the CS-NCC-PL hydrogel group showed a significantly higher hydroxyproline content (60.62 ± 11.46 μg/100 mg) by day 14. Immunohistochemistry results revealed elevated levels of α-SMA and CD31, markers of myofibroblast presence and angiogenesis, peaking at day 7.

These findings suggest that the CS-NCC-PL hydrogel is a promising personalized wound dressing for bedridden patients, offering improved healing outcomes in hospital settings.