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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 prepare cyclosporine A-loaded nanostructured lipid carriers (CsA-NLC) for ocular administration and investigate its physicochemical properties and eye irritation. Methods CsA-NLC was prepared by melt-emulsion method. The optimal prescription was screened by orthogonal experiment. The particle size, morphology, entrapment efficiency, drug loading and release behavior of CsA-NLC in artificial tears were investigated. The dispersion state of CsA in the carrier was confirmed by differential scanning calorimetry (DSC) Rabbits were used to study their eye irritation. Results The majority of CsA-NLC prepared by optimized conditions were spherical (35.9 ± 0.21) nm, Zeta potential (-13.9 ± 0.21) mV, entrapment efficiency and drug loading were 97.5 ± 0.58% And (16.2 ± 0.09) mg.mL-1. DSC shows that the drug is dispersed in the nanoparticles in an amorphous form. CsA-NLC has obvious sustained-release characteristics, in vitro release behavior in line with the single exponential model. CsA-NLC non-irritating to the eyes of rabbits. Conclusion The prepared CsA-NLC has the advantages of small particle size, high drug loading, small irritation and obvious sustained-release characteristics in vitro. It is expected that the controlled release of CsA-NLC will improve the ophthalmic bioavailability of the drug.