State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, PR China.
Biomacromolecules. 2013 Sep 9;14(9):3034-46. doi: 10.1021/bm401131w. Epub 2013 Aug 19.
Poly(vinylcaprolactam) (PVCL)-based biodegradable microgels were prepared for the biomedical application as drug delivery system via precipitation polymerization, where N,N-bis(acryloyl) cystamine (BAC) served as cross-linker, methacrylic acid (MAA) and polyethylene glycol (PEG) methyl ether methacrylate acted as comonomers. The microgels with excellent stability had distinct temperature sensitivity as largely observed in the case of PVCL-based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing MAA content and ambient pH. In the presence of reducing agent glutathione (GSH) or dithiothreitol (DTT), the microgels could be degraded into individual linear polymer chains by the cleavage of the disulfide linkages coming from the cross-linker BAC. The microgels could effectively encapsulate Doxorubicin (DOX) inside and presented stimuli-triggered drug release in acidic or reducing environment. The results of the cytotoxicity assays further demonstrated that the blank microgels were nontoxic to normal cells while DOX-loaded microgels presented efficient antitumor activity to HeLa cells.
聚（乙烯基己内酰胺）（PVCL）基可生物降解的微凝胶通过沉淀聚合被制备用于药物传递系统的生物医学应用，其中 N，N-双（丙烯酰）胱胺（BAC）用作交联剂，甲基丙烯酸（MAA）和聚乙二醇（PEG）甲基醚甲基丙烯酸酯用作共聚单体。所制备的微凝胶具有出色的稳定性，并且在很大程度上表现出明显的温度敏感性，如基于 PVCL 的颗粒，其体积相转变温度（VPTT）随着 MAA 含量和环境 pH 值的增加而升高。在还原剂谷胱甘肽（GSH）或二硫苏糖醇（DTT）的存在下，微凝胶可以通过交联剂 BAC 中的二硫键的断裂被降解成单个线性聚合物链。微凝胶可以有效地将阿霉素（DOX）包封在内部，并在酸性或还原环境中呈现出刺激触发的药物释放。细胞毒性测定的结果进一步表明，空白微凝胶对正常细胞无毒，而负载 DOX 的微凝胶对 HeLa 细胞具有有效的抗肿瘤活性。
