摘要
目的:选择盐酸倍他洛尔为模型药物,制备新型镶嵌蒙脱石载体的离子交换给药系统载药蒙脱石壳聚糖纳米粒(Mt-BH/CS NPs),为新型的眼部混悬剂开发提供参考。方法:采用离子凝胶法制备Mt-BH/CS NPs,利用正交试验优化处方,选取壳聚糖质量浓度,多聚磷酸钠(TPP)浓度、壳聚糖与TPP质量比及盐酸倍他洛尔质量浓度为考察因素,考察Mt-BH/CS NPs的包封率、载药量及体外释放,通过黏附性试验和人永生化角膜上皮细胞的细胞毒性试验考察Mt-BH/CS NPs的生物学性质。结果:最佳处方工艺为壳聚糖质量浓度1.5 g·L^(-1),TPP质量浓度1.2 g·L^(-1),壳聚糖-TPP(10∶1),盐酸倍他洛尔质量浓度2.0 g·L^(-1);Mt-BH/CS NPs平均包封率36.13%,平均载药量14.50%,10 h累积释放率达82.23%。Mt-BH/CS NPs相对于盐酸倍他洛尔水溶液的人永生化角膜上皮细胞毒性较小;Mt-BH/CS NPs与黏膜混合后Zeta电位下降,表明其对黏膜有一定的黏附性。结论:Mt-BH/CS NPs载药量较高、体外释放缓慢、细胞毒性小、生物黏附性大,可望用于眼部疾病的治疗,以期改善新型给药系统的释放性能并增强与眼部的相互作用,从而提高药物的眼部生物利用度并减少不良反应。
Objective： Taking betaxolol hydrochloride as model drug, to prepare drug loading montmorillonite-chitosan nanoparticles by ionic gelation of chitosan with sodium polyphosphate （TPP） , which is known simply as Mt-BH/CS NPs. Method： Mt-BH/CS NPs was prepared by ionic gelation, orthogonal test was adopted to optimize its formulation process by taking encapsulation efficiency and drug loading as indexes. Encapsulation efficiency, drug loading and in vitro release properties of Mt-BH/CS NPs were examined by UV method and its biological properties of nanoparticles suspension were investigated by mucoadhesive test and in vitro cytotoxicity test. Result： The best formulation process was as following： chitosan concentration of 1.5 g·L^-1, TPP concentration of 1.2 g·L^-1 , chitosan-TPP （10 ： 1 ） , betaxolol hydrochloride concentration of 2 g·L^-1. The average encapsulation efficiency of five batches of Mt-BH/CS NPs was 36. 13% and its average drug loading was 14. 50% with RSD 〈 1.0% by dialysis method. The cumulative release rate of Mt-BH/CS NPs was 82.23% in 10 h. In the mucoadhesive test, after mixing with mucous membrane, the reduction of Zeta potential value of Mt-BH/CS NPs indicated that there was mucoadhesive property of Mt-BH/CS NPs. The cell viability of human immortalized corneal epithelial cells after being exposed to betaxolol hydrochloride solution and Mt-BH/CS NPs showed that cytotoxicity of betaxolol hydrochloride solution was higher than that of Mt-BH/CS NPs suspension. Conclusion： Mt-BH/CS NPs has a high drug loading, slow in vitro release, low toxicity and great mucoadhesive property, which may hold promise to be an attractive novel nanosystem for the treatment of ocular diseases. The new drug delivery system can improve the capability of release properties and enhance the interaction with the eye, so as to improve the ocular bioavailability of drugs and reduce their adverse reactions.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2017年第5期12-16,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金青年基金项目(51102052)
广东省医学科学技术研究基金项目(A2016275)
关键词
蒙脱石
盐酸倍他洛尔
壳聚糖
纳米粒
人永生化角膜上皮细胞
多聚磷酸钠
montmorillonite
betaxolol hydrochloride
chitosan
nanoparticles
human immortalized corneal epithelial cells
sodium polyphosphate
