丹皮酚-奥扎格雷偶联物长循环脂质体的制备及其体外释放

Preparation and in vitro release of paeonol-ozagrel conjugate long-circulating liposomes

目的:优化丹皮酚-奥扎格雷偶联物(paeonol-ozagrel conjugate,POC)长循环脂质体的制备处方及工艺,测定其体外释放度。方法:采用乙醇注入法制备POC长循环脂质体,并用正交设计优化该脂质体的制备处方及工艺,透射电镜观测其形态,激光粒度仪测定其粒径及电位,透析法考察脂质体的体外释放。结果:最优处方为胆固醇与大豆卵磷脂的质量比为1∶12; DSPE-PEG2000与大豆卵磷脂的质量比为8∶60;有机相与水相的体积比为2∶10;制备的长循环脂质体为近球形结构,包封率大于95%;平均粒径50 nm左右;体外释放实验结果表明制备得到的脂质体具有缓释作用。结论:POC长循环脂质体制备工艺简单、可行、包封率较高,且与原料药相比具有一定的缓释作用。

Objective: To optimize the preparation and formulation of paeonol-ozagrel conjugate( POC)long circulating liposomes and investigate the release rate in vitro. Methods: POC long-circulating liposomes were prepared by ethanol injection method,and orthogonal design was used to optimize the formulation and preparation process of POC long-circulating liposomes. The morphology of liposomes was observed by transmission electron microscopy,the particle size and potential were determined by laser particle size analyzer,and the release of liposomes in vitro was investigated by dynamic dialysis. Results: The optimal formulation was as follows: the mass ratio of cholesterol to soybean lecithin was 1∶ 12,the mass ratio of DSPE-PEG2000 to soybean lecithin was 8∶ 60,and the volume ratio of organic phase to aqueous phase was 2 ∶ 10. The prepared long-circulating liposomes were nearly spherical in structure,the encapsulation efficiency was more than 95%,and the average particle size was about 50 nm. The results of in vitro release experiments showed that the prepared liposomes had a sustained release effect. Conclusion: The preparation process of POC long-circulating liposomes is simple and feasible with high encapsulation efficiency. POC long-circulating liposomes have a certain sustained-release effect compared with the bulk drug.