维生素A棕榈酸酯阳离子脂质体原位凝胶的制备及其兔角膜滞留性考察

Preparation and in vivo Corneal Retention of Vitamin A Palmitate-loaded Cationic Liposomal In-situ Gel

目的:以维生素A棕榈酸酯(VAP)为主药,制备阳离子脂质体原位凝胶,并对其兔角膜滞留性进行考察。方法:采用薄膜分散法制备VAP脂质体(VAPL),并用不同季铵化程度的NC-三甲基壳聚糖(TMC)包衣制备CAP阳离子脂质体(TMCVAPL),再以泊洛沙姆407为基质,制备VAP阳离子脂质体原位凝胶(TMC-VAPL-ISG)。采用荧光示踪法对其兔角膜的滞留时间进行考察。结果:透射电镜显示VAP脂质体粒径分布均匀,未包衣时平均粒径为(62.98±0.078)nm,Zeta电位为(-11.2±0.57)mV,平均包封率为(70.62±0.66)%(n=3);TMC包衣后,脂质体粒径明显增大(P<0.05),平均包封率为(69.49±0.79)%,随着TMC季铵化程度的增大,Zeta电位显著增大(P<0.05)。与未包衣和包衣的CAPL相比,TMC-CAPLISG兔角膜的滞留时间延长2倍,且随着TMC季铵化程度的提高,滞留效果逐渐增强(P<0.05)。结论:TMC-VAPL-ISG具有阳离子脂质体和原位凝胶的优势,能明显延长兔角膜滞留时间。

Objective： To prepare cationic liposomal in-situ gel with vitamin A palmitate （VAP） as the model drug and investigate the corneal retention in rabbit eyes. Method： VAP liposomes （VAPL） were prepared by the film dispersion method, then coated by Ntrimethyl chitosan （TMC） with different degree of quaternization （DQ） to obtain cationic liposomes （TMC-VAPL）. Poloxamer 407 as the gel base,TMC-VAPL in-situ gel （TMC-VAPL-ISG） was prepared. The residence time in rabbit eyes of TMC-VAPL-ISG was observed with fluorescence tracer method. Result ： Images of TEM showed that the morphology of VAPL was uniform. Before TMC coating, the mean size was （62. 98 ± 0. 078 ）nm, Zeta potential was （-11.2 ± 0. 57 ） mV and mean entrapment efficiency was（ 70. 62 ± 0. 66）% （ n = 3 ）. After TMC coating, the particle size was increased （ P 〈 0. 05 ） and mean entrapment efficiency was （ 69.49 ± 0. 79 ） %. With the increase of DQ,the Zeta potential of TMC-VAPL was enhanced accordingly（P 〈 0. 05 ）. The residence time of TMC-VAPL-ISG was prolonged 2 times compared with that of uncoated and coated VAPL, and as the increase of DQ, the in vivo corneal retention behavior was also improved（ P 〈 0. 05 ）. Conclusion： TMC-VAPL-ISG has the advantages of cationic liposomes and in-situ gel, and can obviously prolong the residence time in rabbit eyes.