环孢素A眼用纳米脂质载体的制备及表征

Preparation and in Vitro Characterizations of Cyclosporine A Ocular Nanostructured Lipid Carriers

目的制备适于眼部给药的环孢素A纳米脂质载体(cyclosporine A-loaded nanostructured lipid carriers,CsA-NLC),并考察其理化性质和眼局部刺激性。方法采用熔融-乳化法制备CsA-NLC,通过正交实验筛选出最优处方。考察CsA-NLC的粒径、形态,包封率、载药量及在人工泪液中的释药行为,采用差示扫描量热法(differential scanning calorimetry,DSC)确证CsA在载体中的分散状态,利用家兔研究其眼局部刺激性。结果优化条件下制备的CsA-NLC多为类球形粒子,平均粒径(35.9±0.21)nm,Zeta电位(-13.9±0.21)mV,包封率、载药量分别为(97.5±0.58)%和(16.2±0.09)mg.mL-1。DSC表明药物以非结晶状分散于纳米粒中。CsA-NLC具有明显的缓释特征,其体外释药行为符合单指数模型。CsA-NLC对家兔眼部无刺激性。结论制备的CsA-NLC粒径小,载药量高,刺激性小,体外释放具有明显的缓释特征,有望实现药物眼部控释递送,提高药物的眼用生物利用度。

OBJECTIVE To develop an appropriate nanostructured lipid carrier （CsA-NLC） for ocular drug delivery of cyclosporine A and its in vitro physicochemical properties and ocular irritation studies were investigated. METHODS The melt-emulsification method was chosen to prepare CsA-NLC. The formulation was optimized by orthogonal design. The morphology of CsA-NLC was observed by transmission electron microscopy （TEM）. The mean particle size and Zeta potential were measured by laser particle size analyzer. The state of drug in NLC was confirmed by DSC. Drug loading and encapsulation efficiency were determined by HPLC. Dialysis method at 34 ℃ was employed to investigate the in vitro release of CsA-NLC. The topical ocular irritation study of CsA-NLC was made in rabbits. RESULTS The obtained CsA- NLC was approximately spherical in shape with average particle size of （35.9±0.21） nm and zeta potential of （-13.9±0.21） mV. The drug loading and encapsulation efficiency were （16.2±0.09）% and （97.5±0.58）%, respectively. The in vitro release of CsA- NLC was slowed down and fitted well single exponential distribution model. There was no irritation for CsA-NLC to rabbits eye. CONCLUSION CsA- NLC with small particle sizes and high drug loading, slow release would be a promising nanocarrier for ocular drug delivery to improve drugs bioavailability.