羧甲基壳聚糖包衣长春西汀纳米脂质体的制备及其体外释药考察

Studies on the formulation and preparation of carboxymethyl chitosan-coated vinpocetine nanoliposomes and their drug release properties in vitro

目的:研制羧甲基壳聚糖(CMC)包衣长春西汀(VIN)纳米脂质体,并对其进行体外释药考察。方法:采用薄膜分散法制备VIN脂质体,用不同取代度的CMC包衣,经高压均质机乳匀得到CMC包衣的VIN纳米脂质体。以包封率为指标,正交试验筛选最佳处方;激光粒度分析仪测定其Zeta电位,粒径大小及分布,并用透射电镜观察其形态;体外透析法考察其体外释药性质。结果:CMC包衣VIN脂质体的最佳处方为药脂比1∶20,胆固醇∶卵磷脂1∶6,甘露醇占总量的50%,CMC的取代度为50%。其形态圆整,包衣效果理想,平均包封率为(72.2±2.4)%,Zeta电位为(-11.6±2.1)mV,平均粒径为(94.8±5.93)nm(n=3);体外释药曲线符合Higuchi方程:Q=-0.35220+0.20628t1/2(r=0.9925)。结论:CMC包衣VIN纳米脂质体包封率较高,达纳米级,体外具显著缓释性质。

OBJECTIVE To study the optimal formulation, preparation and drug release in vitro of the carboxymethyl chitosan （CMC） coated vinpocetine （VIN） nanoliposomes. METHODS VIN liposomes were prepared by the film dispersion method. CMCs with different substitution were used to coat the liposomes followed by extruding through high pressure homog enizer. Orthogonal design was applied and the encapsulation efficiency was chosen as index to screen the optimal formulation. The zeta potential, mean size and size distribution were determined by Zetersizer. Dialysis in vitro was employed to study the drug release from the CMC coated nanoliposomes. RESULTS The optimal formulation of the CMC coated VIN nanoliposomes was as follows： the ratio of VIN and （egg lecithin＋ cholesterol） was 1：20; the ratio of cholesterol and egg lecithin was 1：6; weight percentage of mannitol in the formulation was 50% ; the substituted degree of CMC was 50%. The optimal nanoliposomes had promising appearance and coating layer. The encapsulation efficiency was （72. 2± 2. 4）%, while the zeta potencial and mean size was （-11.6 ± 2. 1 ）mV and （94. 8 ±5. 9）nm, respectively（n = 3）. The drug release in vitro was accorded with the Higuchi equation： Q= -0. 352 20 ＋ 0. 206 28t^1/2 ,r = 0. 992 5. CONCLUSION The CMC coated VIN nanoliposomes had promising encapsulation efficiency, nanometeric sizes and significant sustained-release property in vitro.