以聚乳酸-b-聚乙二醇-b-聚乳酸二丙烯酸酯为交联剂的pH响应型水凝胶的制备及药物控制释放研究

Preparation of pH-responsive hydrogel based on triblock copolymer of polyL-lactate and polyethylene glycol for controlled drug release

采用开环聚合的方法合成了两种不同分子量的聚乙二醇-聚乳酸嵌段共聚物二醇,用丙烯酸酯封端后得到大分子交联剂聚乳酸-b-聚乙二醇-b-聚乳酸二丙烯酸酯(PELAMA)。它们与N-异丙基丙烯酰胺(NIPAM)、丙烯酸(AA)及光引发剂混合后由紫外光引发聚合生成了可生物降解的水凝胶聚乙二醇聚乳酸二丙烯酸酯-丙烯酸-N-异丙基丙烯酰胺(PELAMA-AN)。并对PELAMA-AN进行了表征。研究结果表明:PELAMA-AN在pH=7.4、pH=1.2的条件下,溶胀率分别为1000%~2000%、400%~500%,盐酸阿霉素释放10h的累积释放率分别为20%~40%、50%~60%,并且可以随着pH的变化反复切换。PELAMA-AN具有应用于口服药物载体的潜力。

Two kinds of triblock copolymer diols of poly L-lactate（PLLA）and polyethylene glycol（PEG）were synthesized by ring-opening polymerization.The copolymers were end-capped with methacrylate to form macrocrosslinker poly（L-lactide）-b-polyethylene glycol-b-poly（L-lactide）dimethacrylates（PELAMA）for preparation of pH-responsive hydrogel poly（PLEAMA-Acrylic acid-N-isopropylacrylamide）（PELAMA-AN）through photopolymerization using N-isopropylmethacylamide（NIPAM）,acrylic acid（AA）as monomers.PELAMA was characterized with FT-IR and 1 H-NMR.The swelling ratio of hydrogels in PBS at various pH values was studied.Simultaneously degradation property and the controlled drug release behavior of hydrogels were also investigated.The results showed that PELAMA-ANs were typical pH-responsive hydrogels.The swelling ratio（1000% 2000%）of hydrogels in pH =7.4 PBS was two times bigger than that in acidic environment（pH =1.2）（400% 500%）.Meanwhile,the periodically swelling/diswelling property of the hydrogels was observed by switching the pH values.It was found that the release rate of the doxorubicin hydrochloride at acidic condition（20%40%）was smaller than that in a neutral environment（50%60%）with in 10 h.Also,the hydrogel released drug killed HeLa cells,which indicated that the PELAMA-AN hydrogels had the potential to be used as anticancer drug carriers.