N-三甲基壳聚糖包衣的维生素A棕榈酸酯脂质体的制备及其体外释药

Study on the preparation of vitamin A palmitate liposomes coated by N-trimethyl chitosan and their drug release characteristic in vitro

目的:研制N-三甲基壳聚糖(TMC)包衣的维生素A棕榈酸酯脂质体(VAPL),并对其进行体外释药考察。方法:采用薄膜分散法制备VAPL,合成不同季铵化程度的TMC,并对VAPL进行包衣。以包封率为指标,筛选VAPL最佳处方;用透析法进行体外释药研究。结果:最优处方的TMC包衣VAPL平均包封率为(85.2±3.2)%(n=3)。未包衣VAPL平均粒径为(97.20±0.09)nm,Zeta电位为(-49.1±0.7)mV。TMC包衣后,随着TMC季铵化程度的增大,Zeta电位显著增大(P<0.05);TMC20、TMC40、TMC60包衣脂质体体外释药曲线符合Higuchi方程,分别为Q=4.3408t1/2+4.2295(r=0.9552),Q=4.1116t1/2+3.6312(r=0.9601),Q=3.3418t1/2+3.9545(r=0.9546)。结论:TMC包衣VAPL的制备工艺可行,其表面带有较高正电性,为下一步研究延长角膜滞留时间的释药系统打下基础。

OBJECTIVE To prepare vitamin A palmitate liposomes （VAPL） coated by N-trimethyl chitosan （TMC） and study on their drug release characteristic in vitro. METHODS VAPL were prepared by the film dispersion method. TMCs with different degree of quarternization （DO） were used to coat the liposomes. The encapsulation efficiency was chosen as the index to screen the optimal formulation of the preparation. Dialyzer was employed to study the release of VAP from the liposomes in vitro. RESULTS The mean entrapment efficiency of optimal TMC coated VAPL formulation was （85.2 ± 3.2）% （n = 3）. The mean diameter of VAPL before coating was （97.20 ± 0. 09）nm,and the zeta potential was （ - 49. 1 ± 0. 7）mV. As the increase of DQ of TMC, the zeta potential of TMC-coated VAPL was increased significantly （P〈0. 05）. The VAP release from TMC20,TMC40 and TMC60 - coated VAPL in vitro was accorded with the following Higuchi equation, respectively： Q =4.3408t^1/2＋4.2295（r=0.9552）,Q=4.111 6t^1/2＋3.6312（r=0.9601） and Q=3.341 8t^1/2 ＋3.9545（r=0.9546）. CONCLUSION The preparation of VAPI. coated by different DQ of TMC was feasible. Their positive zeta potential was the basis of the further study on drug release system to prolong corneal retention time.