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Treating Burn Infections With Topical Delivery of Positively Charged Norfloxacin-Loaded Lipid-Polymer Hybrid Nanoparticles.

Kamilia H. A. Mohammed,F. Rasslan,M. A. Abd El-Fattah,Seham M. Shawky,Omnya M. Amin,Heba A. Eassa

Published 2024 in Recent Advances in Drug Delivery and Formulation

ABSTRACT

BACKGROUND 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%. OBJECTIVE 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. METHODS 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. RESULTS 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 24h. 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. CONCLUSION 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.

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