聚乙二醇化壳聚糖-氟尿嘧啶偶合物的制备及体外释放研究

目的 合成聚乙二醇化壳聚糖-氟尿嘧啶偶合物（5-FU-CS-mPEG）,并考察其体外释放性能.方法 以羧基化单甲氧基聚乙二醇（mPEG-COOH）与壳聚糖（CS）反应制得聚乙二醇单甲醚改性壳聚糖（mPEG-CS）,再与经氯乙酸修饰的氟尿嘧啶（FUA）在1-乙基-（3-二甲基氨基丙基）碳酰二亚胺盐酸盐（EDC·HCl）/N-羟基琥珀酰亚胺（NHS）介导下与CS偶联,生成目标产物5-FU-CS-mPEG;用UV、1 H-NMR、FT-IR对结构进行表征;UV法计算前药载药量;采用动态透析法研究前药释放度.结果 经结构确证,成功合成了5-FU-CS-mPEG;经1 H-NMR计算mPEG的取代度为12.31％;载药量为4.83％;大分子前药在120 h的累积释放量为57％.结论5-FU-CS-mPEG具有一定的缓释作用.

Synthesis and research on release behavior of prodrug of 5-FU-CS-mPEG in vitro

Objective To synthesize a prodrug named N-methoxy poly （ethylene glycol ）-grafted-chitosan-5- fluorouracil acetic acid conjugate, and study its release in vitro. Methods mPEG-COOH was firstly combined with chitosan, and then reacted with 5-fluorouracil aceticaeid （FUA） modified with chloroaeetie acid by 1-ethyl- 3 （3-dimethyllaminopropyl） earbodiie hydrochlide （ EDC ~ HC1 ）/N-hydroxysueeinimide （NHS）. The structures were identified by UV, 1H-NMR and FT-IR. The re~ease of the 5-FU-CS-mPEG in vitro was evaluated by using a dialysis method. Results After determination, the reaction product was 5-FU-CS-mPEG. The degrees of substitution of mPEG were 12.31% ,and the drug-loading rate was 4.83%. The total release was 57% in 120 h. Conclusion 5-FU-CS-mPEG can be used as a new carrier for sustained release drug systems.