Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran, Iran.
Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran.
J Biomed Mater Res A. 2019 Oct;107(10):2327-2339. doi: 10.1002/jbm.a.36741. Epub 2019 Jun 22.
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.
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。