酸解离温敏性水凝胶药物载体在肿瘤治疗中的应用

Application of acid dissociable thermosensitive hydrogel based drug carrier on tumor treatment

文章通过可逆加成-断裂链转移(reversible addition-fragmentation chain transfer,RAFT)聚合制备一种酸解离温敏性嵌段聚合物水凝胶聚(N-异丙基丙烯酰胺130)-原酸酯-聚乙二醇90-原酸酯-聚(N-异丙基丙烯酰胺130),命名为POP,并研究其作为药物载体对化疗药物阿霉素(Dox)的释放以及对肿瘤的治疗效果。采用核磁共振氢谱(proton nuclear magnetic resonance,1H NMR)和凝胶渗透色谱(gel permeation chromatography,GPC)对POP聚合物的结构及分子量进行表征;采用旋转流变仪分析水凝胶的温敏性;采用扫描电子显微镜(scanning electron microscope,SEM)观察水凝胶的微观结构,并进行酸解离性分析;采用紫外分光光度法考察水凝胶的体外药物释放行为;采用苏木精-伊红染色法(hematoxylin-eosin staining,H&E)研究水凝胶对小鼠体内主要器官的毒性以及载药水凝胶对肿瘤的抑制效果。实验结果表明,POP水凝胶呈现规整的三维网状孔道结构,具有良好的酸解离性和温敏性,可作为阿霉素的载体,稳定持久释放药物,有效地抑制肿瘤的生长。

In this paper,the acid dissociable thermosensitive block polymer hydrogel(poly(N-isopropylacrylamide 130)-ortho ester-polyethylene glycol 90-ortho ester-poly(N-isopropylacrylamide 130),named POP)was prepared by reversible addition-fragmentation chain transfer(RAFT)polymerization,and its use as a drug carrier to release the chemotherapy drug doxorubicin(Dox)and its therapeutic effect on tumors were explored.The structure and molecular weight of POP polymers were characterized by proton nuclear magnetic resonance(1H NMR)and gel permeation chromatography(GPC);the temperature sensitivity of the hydrogel was investigated by rotational rheometer;the microstructure and the acid dissociation of the hydrogel were investigated by scanning electron microscope(SEM);UV spectrophotometry was used to explore the drug release behavior of the hydrogel in vitro;the hematoxylin-eosin staining(H&E)was used to study the toxicity of the hydrogel to the main organs in mice and the inhibitory effect of the hydrogel on tumors.The experimental results showed that the POP hydrogel presented a regular three-dimensional pore network structure,and had good acid dissociability and temperature sensitivity,which can be used as a carrier for Dox and effectively inhibit the growth of tumors by stable and long-lasting drug release.