Ciprofloxacin (CIP), a widely used antibiotic, is a poor biopharmaceutical resulting in low bioavailability. We optimized a CIP polymer–lipid hybrid nanoparticle (CIP-PLN) delivery system to enhance its biopharmaceutical attributes and the overall therapeutic performance. CIP-PLN formulations were prepared by a direct emulsification–solvent–evaporation method. Varying the type and ratio of lipid was tried to optimize a CIP-PLN formulation. All the prepared formulations were evaluated for their particle size, polydispersity index, zeta potential, physical stability, and drug entrapment efficiency. The drug in vitro release profile was also studied. Antibacterial activities were tested by the agar diffusion method for all CIP-PLN formulations against an Escherichia coli clinical bacterial isolate (EC04). CIP-PLN formulations showed average sizes in the range of 133.9 ± 1.7 nm to 217.1 ± 0.8 nm, exhibiting high size uniformity as indicated by polydispersity indices lower than 0.25. The entrapment efficiency was close to 80% for all formulations. The differential scanning calorimetry (DSC) thermograms indicated the existence of CIP in the amorphous state in all PLN formulations. Fourier transform infrared spectra indicated deep incorporation of molecular CIP within the polymer matrix. The release profile of CIP from PLN formulas showed a uniform prolonged drug profile, extended for a week from most formulations with a zero-order kinetics. The antibacterial activity of CIP-PLN formulations showed significantly higher antibacterial activity only with F4 containing lecithin as the lipid component. In conclusion, we successfully optimized a CIP-PLN formulation with a low nanoparticle size in a close range, high percentage of entrapment efficiency and drug loading, uniform prolonged release rate, and higher antibacterial activity against the EC04 clinical isolate.

环丙沙星 (CIP) 是一种广泛使用的抗生素，是一种较差的生物药物，导致生物利用度低。我们优化了 CIP 聚合物-脂质杂化纳米颗粒 (CIP-PLN) 递送系统，以增强其生物制药属性和整体治疗性能。CIP-PLN 配方是通过直接乳化-溶剂-蒸发法制备的。尝试改变脂质的类型和比例来优化 CIP-PLN 配方。对所有制备的制剂的粒度、多分散指数、zeta 电位、物理稳定性和药物包封率进行了评估。还研究了药物的体外释放曲线。通过琼脂扩散法测试了所有 CIP-PLN 制剂对大肠杆菌的抗菌活性临床细菌分离物 (EC04)。CIP-PLN 配方的平均粒径范围为 133.9 ± 1.7 nm 至 217.1 ± 0.8 nm，如多分散指数低于 0.25 所示，显示出高粒径均匀性。所有配方的包封率接近 80%。差示扫描量热法 (DSC) 热谱图表明所有 PLN 配方中都存在无定形状态的 CIP。傅里叶变换红外光谱表明分子 CIP 在聚合物基质中的深度结合。PLN 配方中 CIP 的释放曲线显示出均匀的延长药物曲线，从大多数零级动力学配方中延长了一周。CIP-PLN 制剂的抗菌活性仅在含有卵磷脂作为脂质成分的 F4 时显示出显着更高的抗菌活性。综上所述，