阿昔洛韦眼用壳聚糖纳米粒的制备及家兔生物利用度研究

Acyclovir-loaded chitosan nanoparticles preparation and ocular drug bioavailability investigation

目的:应用离子交联法制备阿昔洛韦壳聚糖纳米粒,考察其体外性质及其经家兔眼部给药后的生物利用度。方法:壳聚糖与三聚磷酸钠通过离子交联作用制备纳米粒,考察了纳米粒的粒径、Zeta电位、包封率以及体外释放性质,通过家兔眼部结膜囊内给药,考察眼房水中药物浓度的变化,并与市售阿昔洛韦滴眼液相比较。结果:阿昔洛韦壳聚糖纳米粒的平均粒径为235nm,多分散系数为0.256,Zeta电位为43.9 mV;平均包封率为15.6%,平均载药量为1.9%;家兔眼部给药后,AUC0→6h达到3.69μg.h-1.mL-1,是市售制剂的2.4倍。结论:实验初步证实制备的壳聚糖纳米粒可以促进阿昔洛韦的眼部吸收。

Aim：To prepare acyclvir-loaded chitosan nanoparticles （ALCN） and evaluate its pharmacokinetic characterization in vitro and in vivo. Methods： ALCN were prepared by a ion-connection process between chitosan and sodium tripolyphosphate. The effects of dispersion phase type and amount of drug on the characterizations of the ALCN such as the mean size, zeta potential, drug entrapment efficient（ EE）, loading capacity（LC） and drug release were investigovted. In vivo experiments were carried out on male New Zealand rabbits. The acyclovir levels in aqueous humor were monitored for 6 hours, compared with the acyclovir eye drops. Results： The mean size of the nanoparticles was 235nm with the polydispersity index of 0. 256 and the zeta potential was 43.9 mV. The mean entrapment efficiency and loading capacity were 15.6% and 1.9%, respectively. The AUC0→6h reached 3.69μg·h^-1·mL^-1, 2.4 - fold of the eye drops. Conclutions： Chitosan nanoparticles could promote the absorption of acyclovir and can be proposed as a potential ophthalmic delivery system.