洛伐他汀长循环脂质体的制备及性质研究

Preparation and Characterization of Lovastatin-loaded Liposomes

目的:研制洛伐他汀长循环脂质体,考察其制备的影响因素,优化处方工艺,并对其理化性质和释放行为进行表征。方法:以PEG2000作为表面修饰剂,采用薄膜分散法制备了洛伐他汀长循环脂质体。采用微柱离心法测定包封率并结合粒径,在单因素考察的基础上,通过正交设计对处方和工艺进行优化,确定了洛伐他汀长循环脂质体的最佳处方及制备工艺。结果:制得的洛伐他汀长循环脂质体外观圆整,大小均一,可清晰看到指纹状结构,较普通脂质体更为不规则,平均粒径为(115.6±0.3 nm),Zeta电位为(-14.41±0.57 m V),载药量为(100±2.9 g/m L),包封率80%以上。用透析法考察了洛伐他汀长循环脂质体的体外释药行为,结果表明洛伐他汀长循环脂质体释放稍快于普通脂质体。

Objective： to prepare Lovastatin-loaded liposomes （L-LTL）, to study the influencing factors, to optimize their formulation and to characterize their properties and release behaviour. Methods：Lovastatin was encapsulated into liposomes coated with PEG2000, called long-circulating Lovastatin-loaded liposomes （L-LTL）. L-LTL was prepared by thin film hydration method. Lovastatin and long-circulating liposomes were separated by mini-column centrifugation .Based on the test of single factor and by the index of size and entrapment efficiency, the formulation and the preparation techniques of L-LTL were optimized by Orthogonal Design. Results： The size and Zeta potential of L-LTL was determined by Zeta Plus. The long-circulating liposomes appeared round, uniform in size, possessed fingerprint structure,was more irregular than liposomes. The average size of liposome was about 115 nm and the Zeta potential absolute value was about 20 mV. The results indicated that the drug-loading was 100-x2.9 g/mL and the entrapment efficiency of L-LTL achieved more than 80 %.The profile of Lovastatin release from L-LTL was studied by dialysis. The curve fitting method was used to find the drug release equation. The results showed that the drug release of L-LTL in vitro fit Higuchi equation well.