盐酸左氧氟沙星眼用纳米粒温敏凝胶的制备及体外释放考察

Preparation and in vitro Release of Levofloxacin Hydrochloride Ocular Nanoparticles Thermo-sensitive in situ Gels

目的制备盐酸左氧氟沙星眼用纳米粒温敏凝胶,考察其体外释药行为。方法采用离子交联法制备眼用盐酸左氧氟沙星壳聚糖纳米粒,以泊洛沙姆407和188为温敏基质,以人工泪液稀释前后的胶凝温度为评价指标,采用二因素五水平的中心复合设计-响应曲面法优选温敏凝胶处方,释放度检测法考察该处方的体外释药性。结果载药纳米粒的平均粒径为(60.7±5.1)nm,包封率为(62.5±1.8)%,载药量为(10.43±0.30)%;最佳温敏凝胶基质组成为泊洛沙姆407∶泊洛沙姆188(22%∶6%),胶凝温度为(32.3±0.2)℃,载药纳米粒温敏凝胶24h释放总量达71.9%。结论盐酸左氧氟沙星纳米粒温敏凝胶结合纳米粒和原位凝胶的优点,具有理想的胶凝温度和缓释效果,有望成为眼部给药新剂型。

Objective To prepare ocular levofloxacin hydrochloride nanoparticles thermo-sensitive in situ gels(LVFX-NPs-TISG)and to study its drug release in vitro. Methods Ocular levofloxacin hydrochloride nanoparticles were prepared by ionic cross-linking method. Poloxamer 407 and 188 were used as the thermo-sensitive material. A central composite design-response surface method(CCD-RSM)was adopted to optimize formulation of gel by measuring gelation temperatures with and without artificial tears. A release method was used to study the drug release in vitro. Results The mean diameter of drug loaded nanoparticles was(60.7±5.1)nm. The encapsulation efficiency and drug loading were(62.5±1.8)%and(10.43±0.30)%. The optimized formula was selected as poloxamer 407∶poloxamer 188(22%∶6%)and the gelation temperature was(32.3±0.2)℃. Within 24 hours,accumulative release of levofloxacin hydrochloride was 71.9%. Conclusions LVFX-NPs-TISG showed the advantages of nanoparticles and in situ gels with the properties of desired gelation temperature and sustained drug release in vitro,which hopefully provides a promising ophthalmic drug delivery of levofloxacin hydrochloride.