一种可口服使用的壳聚糖季铵盐紫杉醇纳米粒研制

Paclitaxel Conjugated Trimethyl Chitosan Nanoparticles as Potential Drug Delivery Systems for Cancer Therapy Via Oral Administration

设计并制备壳聚糖季铵盐-紫杉醇纳米粒(TP NPs),用于口服递送抗肿瘤药物紫杉醇(PTX).以30ku和200ku壳聚糖合成壳聚糖季铵盐,并进一步与PTX通过生理条件下可断裂的化学键共价连接,分别命名为TP(30)和TP(200).两亲性TP(30)和TP(200)载药量约为11%,且在水中可自组装形成粒径分布均一的纳米粒(TP(30)NPs和TP(200)NPs).TP(30)NPs和TP(200)NPs平均粒径分别为166.2nm和193.7nm,且可在pH 7.4磷酸盐缓冲液中持续缓慢释放药物达10d.TP(30)NPs和TP(200)NPs的小肠黏膜黏附力均显著高于壳聚糖季铵盐.促渗透作用的研究结果表明TP(30)NPs和TP(200)NPs可显著提高PTX的离体小肠转运,表观渗透系数分别为游离PTX的13.1和6.1倍.因此,本研究中的TP NPs有望用于口服递送抗肿瘤药物.

Paclitaxel （PTX） conjugated trimethyl chitosan nanoparticles （TP NPs） were developed through a cleavable linker for oral delivery of PTX. Chitosan with 30 and 200 ku was used to synthesize trimethyl chitosan and then prepare TP （30） and TP （200）. As the amphiphilie conjugates, TP （ 30 ） and TP （200） containing approximately 11% PTX could self-assemble into nanopartieles with average sizes of 166. 2 and 193. 7 nm, respectively. TP NPs presented a sustained release of PTX for 10 days under physiological condition（pH7. 4）. TP（30） NPs and TP（200） NPs enhanced mueoadhesion in comparison to trimethyl ehitosan, and improved ex vivo intestinal transport of PTX compared with PTX solution by 13. 1 and 6. 1 folds, respectively. Therefore, the self- assembled TP NPs may be promising candidates for cancer therapy via oral administration.