鬼臼毒素纳米靶向制剂的制备与理化性质评价

Preparation and Evaluation of Physicochemical Property of Podophyllotoxin Conjugated Stearic Acid Grafted Chitosan Oligosaccharide Micelles

目的探讨鬼臼毒素纳米靶向制剂的制备方法及评价其质量。方法采用碳二亚胺为耦联剂,合成硬脂酸-壳寡糖嫁接物,采用三硝基苯磺酸法测定载体中氨基取代度,以透析法制备鬼臼毒素载药聚合物胶团,考察载药胶团的粒径、表面电位、药物含量、包封率,释药行为以评价其质量。结果鬼臼毒素纳米靶向胶团粒径为30.8~48.3 nm,随着胶团载药量的增大,粒径逐渐增大,并且随着投药量的增加表面电荷逐渐升高,具有较高的包封率和载药量,鬼臼毒素的投药量为10%时,包封率达69.31%,可明显延缓药物的释放,释放速度随投药量减少而加快。结论鬼臼毒素纳米靶向制剂制备工艺简单,质量较理想。

Objective To explore quality of the podophyllotoxin conjugated stearic acid grafted chitosan oligosaccharide micelles(PPT-CSO-SA)and the preparation process.Methods Stearic acid grafted chitosan oligosaccharide(CSO-SA)was synthesized by the EDC-mediated coupling reaction between carboxyl group of stearic acid(SA)and amine groupsof chitosan oligosaccharide(CSO).The substitution degree of amino groups were determined by TNBS method.PPT-CSO-SA was prepared using a dialysis method.The quality of PPT-CSO-SA through micellar size and the zeta potential,the drug encapsulation efficiency,drug release profiles was evaluated.Results PPT-CSO-SA size was from 30.8 nm to 48.3 nm.The micellar size and the zeta potential increased with increasing charged amounts of drug.The drug encapsulation efficiency could reach a higher level.The highest drug entrapment efficiency could reach 69.31%when the drug feeding ratio was 10%.The cumulative release percentage of PPT from micelles enhanced with decreasing PPT content in the micelles.Conclusion PPT-CSO-SA can be prepared in a simple way and has a good quality.