Gu Chunhua, Le Vanminh, Lang Meidong, Liu Jianwen
Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Colloids Surf B Biointerfaces. 2014 Apr 1;116:745-50. doi: 10.1016/j.colsurfb.2014.01.026. Epub 2014 Jan 25.
Biodegradable graft copolymer, chitosan-graft-poly(ɛ-caprolactone) (CS-g-PCL) was synthesized via ring opening polymerization and characterized by (1)H NMR and FTIR spectroscopy. Then graft copolymers were self-assembled into micelles as drug delivery system. To evaluate drug-polymer compatibility, the Flory-Huggins interaction parameter between 5-fluorouraci (5-Fu) and hydrophobic segment was calculated. The result was in agreement with experimental data from drug loading content and drug loading efficiency. Meanwhile, DLS and TEM were utilized to evaluate the trend of particle size and morphology in aqueous solution with different repeating units of ɛ-CL. The in vitro drug release data was fitted with three kinetic models, usually applied in the drug delivery system. Results indicated that the release of 5-Fu was controllable and the release half-time could reach as long as 54.46 h, much slower than that of free 5-Fu. Cytotoxicity evaluation and cellular apoptosis study suggested good biocompatibility of CS-g-PCL micelles. Moreover, 5-Fu loaded micelles could delay the release of drug and exert comparable cytotoxicity against A549 cells.
通过开环聚合法合成了可生物降解的接枝共聚物壳聚糖-接枝-聚（ε-己内酯）（CS-g-PCL），并通过¹H NMR和FTIR光谱对其进行了表征。然后将接枝共聚物自组装成胶束作为药物递送系统。为了评估药物与聚合物的相容性，计算了5-氟尿嘧啶（5-Fu）与疏水链段之间的Flory-Huggins相互作用参数。结果与载药量和载药效率的实验数据一致。同时，利用动态光散射（DLS）和透射电子显微镜（TEM）来评估具有不同ε-CL重复单元的水溶液中粒径和形态的变化趋势。体外药物释放数据采用三种通常应用于药物递送系统的动力学模型进行拟合。结果表明，5-Fu的释放是可控的，释放半衰期可达54.46小时，比游离5-Fu的释放速度慢得多。细胞毒性评估和细胞凋亡研究表明CS-g-PCL胶束具有良好的生物相容性。此外，载有5-Fu的胶束可以延迟药物释放，并对A549细胞发挥相当的细胞毒性。
