Preparation and characterization of novel, mucoadhesive ofloxacin nanoparticles for ocular drug delivery

The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation, resulting in low ocular bioavailability. Mucoadhesive chitosan (CS)/ tripolyphosphatesodium (TPP) and chitosan (CS)/ tripolyphosphatesodium (TPP)-alginate (ALG) nanoparticles were investigated for the prolonged topical ophthalmic delivery of ofloxacin. A modified ionotropic gelation method was used to produce ofloxacin-loaded nanoreservoir systems. The ofloxacin-loaded CS/TPP and CS/TPP-ALG nanoparticles were characterized for particle size, morphology, zeta potential, encapsulation efficiency, subsequent release and corneal penetration study. The designed nanoparticles have a particle size from 113.8 nm to 509 nm and zeta potential from 16.2 mV to 40.3 mV and encapsulation efficiency values ranging from 19.7% to 33.1%. Nanoparticles revealed a release during the first hours, followed by a more gradual drug release. The ofloxacin-loading CS/TPP or CS/TPP-ALG NPs developed are pronounced penetration enhancing effect as compared to OFX solution (5-6.5 times). Thus, these nanoparticles have a strong potential for ocular drug delivery.

传统眼部制剂的药效受限于角膜滞留能力与渗透性能不足，导致眼部生物利用度偏低。本研究以氧氟沙星（ofloxacin）的延长型眼部局部递送为目标，考察了黏膜黏附型壳聚糖（chitosan, CS）/三聚磷酸钠（tripolyphosphate sodium, TPP）及CS/TPP-海藻酸钠（alginate, ALG）纳米粒的应用潜力。采用改良离子凝胶法制备载氧氟沙星纳米储库系统，并对所得载氧氟沙星CS/TPP与CS/TPP-ALG纳米粒进行表征，表征指标涵盖粒径、形貌、Zeta电位（zeta potential）、包封率、体外释药行为及角膜渗透性能。所制备的纳米粒粒径介于113.8 nm至509 nm之间，Zeta电位为16.2 mV至40.3 mV，包封率范围为19.7%~33.1%。该类纳米粒呈现出初始数小时内的突释行为，随后转为更为平缓的药物释放模式。与氧氟沙星溶液相比，所开发的载氧氟沙星CS/TPP或CS/TPP-ALG纳米粒（nanoparticles, NPs）具有显著的渗透增强作用，渗透效率可达溶液组的5~6.5倍。综上，此类纳米粒在眼部药物递送领域具备极高的应用潜力。