5-氟脲嘧啶载O-羧甲基壳聚糖自组装pH敏感纳米粒的体外释放

Self-Assembled Nanoparticles Based on 5β-Cholanic Acid/O-Carbohydrate Chitosan/Sulfonamide as a Novel Carrier for 5-Fluorouracil

为了提高抗癌药物5-氟脲嘧啶(5-FU)对肿瘤细胞的靶向性及选择性,采用超声-透析法制备了具有pH敏感性的纳米药物载体5β-胆烷酸/O-羧甲基壳聚糖/磺胺地托辛(5β-CHA/OCMC/SDM)自组装水凝胶纳米粒,并用同样的方法将5-FU包载于纳米载体中进行体外释放研究。利用紫外分光光度计于269nm波长下检测5-FU的载药量和包封率以及释放浓度。结果表明,对于5β-CHA/OCMC/SDM纳米粒,药载比(药物和载体的质量比)增加到0.6时,载药量和包封率分别高达51.3%和85.4%。体外释药结果表明,在pH=7.4(人体正常组织的pH值)的磷酸盐缓冲溶液中,接枝5β-CHA的OCMC水凝胶纳米粒对5-FU具有良好的缓释效果,且随接枝量的增加缓释效果增强。pH<6.8(肿瘤组织的pH值)时,接枝SDM的载药纳米粒迅速聚集并强烈释放,表现出良好的pH敏感性。

In order to improve the cancer-targeting and selectivity of antineoplastic agent 5-fluorouracil （5-FU）, a novel pH-responsive drug delivery system [5β-cholanic acid/O-carboxylmethyl chitosan/sulfonamide （5β-CHA/OCMC/SDM）] was synthesized by a diafiltration method. 5-FU was loaded into the self-assembled nanoparticles of 5β-CHA/OCMC/SDM by the same method. The loading content, loading efficiency and the concentration of the released 5-FU were monitored at the wave length of 269 nm on the UV/Vis spectrophotometer. The results show that, as the feed ratio （mass ratio of drug/carrier） was increased to 0.6, the loading content and loading efficiency of the 5β-CHA/OCMC/SDM nanoparticles reach to as high as 51.3% and 85.4%, respectively. The drug release experiments were carried out in vitro and the results show that, in PBS at pH 7.4 （which equals to the pH value of the normal body fluid） the 5β-CHA modified OCMC nanoparticles have good sustained-release effect on 5-FU, which will be enhanced with increasing the degree of substitution of 5β-CHA. Below pH 6.8 （which is close to the pH of tumors） the loaded nanoparticles bearing SDM show good pH sensitivity by shrinking and aggregating and increasing the release rate significantly.