伏立康唑N-三甲基壳聚糖包衣脂质体的制备及体外性质考察  

Study on the Preparation and in vitro Properties of N-Trimethyl Chitosan-coated Liposomes Containing Voriconazole

作　　者：杜修桥[1] 王军[2] 

机构地区：[1]枣阳市第一人民医院药剂科,湖北枣阳441200 [2]武汉大学人民医院药学部

出　　处：《中国药师》2018年第9期1577-1581,共5页China Pharmacist

摘　　要：目的:制备N-三甲基壳聚糖(TMC)包衣伏立康唑(VCZ)脂质体冻干品,对其体外性质进行考察。方法:采用薄膜分散法制备VCZ脂质体(VCZL),以季铵化程度60%的TMC(TMC60)对其进行包衣。处方采用正交试验进行优化,并筛选出最优的冻干保护剂制备冻干品。考察其形态、粒径及Zeta电位,并用透析袋法研究体外释药特性。结果:TMC60包衣VCZL最优处方组成为质量比卵磷脂∶胆固醇4∶1,药物∶类脂1∶20,TMC60溶液浓度为0.15 mg·ml^(-1),PBS的p H为7.4。TMC60包衣VCZL形态圆整,平均粒径为(590.4±16.0)nm,冻干复水化后平均粒径为(503.2±20.5)nm;VCZL的Zeta电位为-46.4 m V,TMC60包衣后为+54.9 m V,冻干复水化后为+52.6 m V;冻干前后平均包封率无明显变化;体外释药符合Higuchi方程。结论:TMC60包衣VCZL粒径均匀,带正电荷,包封率较高,具有缓释性,冻干对其主要性质无显著影响。Objective： To prepare the lyophilized product of N-trimethyl chitosan-coated voriconazole （VCZ） liposomes （VCZL） and study the in vitro properties. Methods： The VCZL was prepared by a film-dispersion method and coated by N-trimethyl chitosan with quaternization degree of 60% （TMC60）. The formula was optimized by orthogonal test and the optimal freeze-drying protective a- gent was screened out. The morphology, size and zeta potential were studied. The in vitro drug release was investigated by a dialysis bag method. Results： The optimal formula of TMC60-coated VCZL was as follows ： the quantity ratio of lecithin to cholesterol was 4 ： 1, the quantity ratio of VCZ to lipids was 1 ： 20, the concentration of TMC60 solution was 0.15 mg . m1-1 and the pH value of PBS was 7.4. The morphology of TMC-60-coated VCZL was spherical with average size of （590.4 ± 16.0） nm, and that of the lyophilized product after rehydration was （503.2 ±20.5 ） nm; the zeta potential of VCZL was - 46.4 mV, that of TMC60-coated VCZL was ＋ 54.9 mV, and that of the lyophilized product after rehydration was ＋ 52.6 mV ; the average entrapment efficiency was stable after the lyophilization; the in vitro drug release was accorded with Higuchi equations. Conclusion： TMC60-coated VCZL is with uniform size, positive charge, high entrapment efficiency and obvious sustained release in vitro, and lyophilization has no notable influence on the properties in vitro.

关 键 词：伏立康唑 N-三甲基壳聚糖 制备 冻干 体外性质 

分 类 号：R944.9[医药卫生—药剂学]