阿糖胞苷多囊脂质体的制备及体外释放度考察

目的制备阿糖胞苷多囊脂质体,并考察其体外释放特性。方法采用复乳法制备阿糖胞苷多囊脂质体;RP-HPLC法测定含量、包封率和体外释放特性;以包封率为指标,单因素及正交试验筛选、优化工艺和处方;光学显微镜下观察多囊脂质体形态;以激光粒度测定仪测定粒径。结果一次乳化时间为8 min、氮气流速为0.3 m3.h-1时包封率最高;优化处方中二油酰磷脂酰胆碱(DOPC)、二棕榈酰磷脂酰甘油(DPPG)、胆固醇(CH)、三油酸甘油酯(TO)的质量浓度分别为10、2、7.5、4 g.L-1,赖氨酸浓度为40 mmol.L-1,有机溶剂选择氯仿-乙醚(体积比1∶1)。阿糖胞苷多囊脂质体在400倍显微镜下形态光滑、圆整,内部呈蜂窝状,无磷酯碎片;平均粒径19.49μm,跨距0.91;包封率达70%以上;以人空白血浆为释放介质,两周释放药物约60%。结论制备的阿糖胞苷多囊脂质体外观良好,包封率较高,体外释放试验表明药物缓慢释放,无突释现象。

Preparation and its release in vitro of multivesicular liposomes containing cytarabine

Objective To study the preparation of multivesicular liposomes containing cytarabine and its sustained-release in vitro. Methods Multiple emulsion method was employed to prepare multivesicular liposomes (MVLs) containing cytarabine. The contents, encapsulation efficiency and release in vitro were determined with RP-HPLC. In order to elevate encapsulation efficiency, the formula and processing were sieved and optimized by single factor or orthogonal design. The MVLs particles were characterized by their morphology which was observed at 400 magnification using a digital biological microscope, and the mean diameter was determined with a Laser diffraction particle size analyzer. Results When the first mixing time was 8 min and the flow rate of nitrogen gas was 0.3 m3·h^-1, encapsulation efficiency percent was the highest. The optimal formula was that: the concentration of 1,2-dioleoyl-sn-glycero-3- phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG), cholesterol (CH) and 1,2,3-trioleoyl-sn-glycerol (TO) were 10 g·L-1, 2 g·L^-1, 7.5 g·L^-1 and 4 g·L^-1, respectively; organic solvent was selected as chloroform-diethyl ether (V︰V=1︰1) and the concentration of L-lysine was 40 mmol·L^-1.The light micrograph at 400 magnification showed that particles were MVLs particles with smooth, spherical, and multivesicular nature, and there was no debris. The mean particle size of MVLs was 19.49 μm and span was 0.91. Encapsulation percent could be higher than 70%. The cytarabine of MVLs released 60 % within two weeks in blank human plasma. Conclusions The appearance of multivesicular liposomes containing cytarabine is fine, and the encapsulation efficiency percent is higher. The release profile shows that the drug is sustained-released, and no abrupt release is found.