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新型双响应半互穿聚合物网络水凝胶用于控制抗癌药物释放。

Novel dual-responsive semi-interpenetrating polymer network hydrogels for controlled release of anticancer drugs.

机构信息

Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran, Iran.

Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran.

出版信息

J Biomed Mater Res A. 2019 Oct;107(10):2327-2339. doi: 10.1002/jbm.a.36741. Epub 2019 Jun 22.

Abstract

Novel dual-responsive hydrogels of semi-interpenetrating polymer networks (semi-IPNs) based on temperature-sensitive N-isopropylacrylamide (NIPAA) and pH-sensitive N-ethylmaleamic acid (NEMA) monomers and sodium alginate polymer were synthesized using free-radical polymerization in the presence of N,N'-methylenebisacrylamide as a crosslinker. Stimuli-responsive properties of the semi-IPN hydrogels showed remarkable sensitivity to both temperature and pH without limitation in NEMA content. Doxorubicin hydrochloride (DOX) as a model drug was efficiently loaded into the hydrogels and the release profiles of drug from them were investigated. The results of in vitro studies showed a quick DOX release in the conditions simulating tumor environment (phosphate-buffered saline [PBS], pH 6.5, 37°C) or endosomes/lysosomes (PBS, pH 5.5, 37°C) compared to simulated human physiological conditions (PBS, pH 7.4, 37°C). In conclusion, the novel poly(NIPAA-co-NEMA) semi-IPN hydrogels could be a promising candidate for targeted and controlled release of anticancer drugs in drug delivery system.

摘要

新型温敏型 N-异丙基丙烯酰胺(NIPAA)和 pH 敏感型 N-乙基马来酰胺酸(NEMA)单体与海藻酸钠聚合物的半互穿聚合物网络(半 IPN)双重响应水凝胶是通过自由基聚合在 N,N'-亚甲基双丙烯酰胺作为交联剂存在的条件下合成的。半 IPN 水凝胶的刺激响应特性对温度和 pH 均具有显著的敏感性,而不受 NEMA 含量的限制。盐酸阿霉素(DOX)作为模型药物被有效地载入水凝胶中,并对其药物释放曲线进行了研究。体外研究结果表明,与模拟人体生理条件(PBS,pH 7.4,37°C)相比,在模拟肿瘤环境(PBS,pH 6.5,37°C)或内涵体/溶酶体(PBS,pH 5.5,37°C)条件下,DOX 的释放速度更快。总之,新型聚(NIPAA-co-NEMA)半 IPN 水凝胶有望成为药物传递系统中抗癌药物靶向控制释放的候选材料。

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