Mohammed Kamilia H A, Rasslan Fatma, Abd El-Fattah Marwa A, Shawky Seham, Amin Omnya M, Eassa Heba A
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11884, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
Recent Adv Drug Deliv Formul. 2025;19(2):142-155. doi: 10.2174/0126673878316672241122041157.
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, -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 and 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.
诺氟沙星（NFX）是一种广谱抗菌剂，但存在水溶性低和首过代谢的问题。这使其口服生物利用度降低了60%-70%。
本研究旨在制备负载诺氟沙星的脂质聚合物杂化纳米粒（NFX-LPHNPs）的外用凝胶，结合脂质体和聚合物纳米粒的优点以克服上述问题。
使用Precirol ATO（脂质）和Eudragit RL100（聚合物）制备NFX-LPHNPs制剂。对其粒径、分布均匀性、包封率、zeta电位和体外释放进行表征。采用Box-Behnken设计依次研究不同变量对材料属性的影响。然后对优化后的配方进行重新评估，并将其制成羟丙甲纤维素凝胶制剂。对该凝胶制剂的物理性质、释放情况和抗菌活性进行评估。
NFX-LPHNPs的粒径范围为28.92至730.30 nm。颗粒分布均匀，表面带正电荷（zeta电位值为+3.91至+60.2 mV）。制剂在8小时内的药物累积释放率为87.9%-100%。优化后的配方显示，实测响应与预测响应拟合良好，粒径为159 nm，释放率为92.61%，包封率为79.2%。凝胶制剂在24小时内呈现持续释放。对金黄色葡萄球菌和铜绿假单胞菌的抗菌测试表明，与单纯负载诺氟沙星的凝胶相比，NFX-LPHNPs对这些病原体的活性增强。
这些结果表明脂质-聚合物杂化纳米粒在提高诺氟沙星对烧伤感染中常见耐药病原体的活性方面具有巨大潜力。此外，局部应用有助于克服诺氟沙星口服相关的问题。
