Luan Shujuan, Zhu Yingchun, Wu Xiaohe, Wang Yingying, Liang Fengguang, Song Shiyong
Institute of Pharmacy, Pharmaceutical College of Henan University, North Jinming Road, Kaifeng 475004, China.
Orthopedics Department of Huaihe Hospital, Henan University, No. 8 Baobei Street, Kaifeng 475000, China.
ACS Biomater Sci Eng. 2017 Oct 9;3(10):2410-2419. doi: 10.1021/acsbiomaterials.7b00444. Epub 2017 Sep 1.
A natural polysaccharide-based nanogel has been synthesized and characterized as pH-sensitive drug delivery system for poorly water-soluble anticancer drugs. In this work, methacrylated hyaluronic acid (MAHA) was used to prepared acid degradable nanogels by a surfactant-free polymerization method in water, where 2,2-dimethacroyloxy-1-ethoxypropane (DMAEP) served as a pH labile cross-linker. Nanogels of different cross-linking density were prepared and doxorubicin (DOX) was successfully encapsulated into the nanogels with drug-loading contents (DLC) ranging from 7.67 to 12.15%. An accelerated DOX release was found in acidic conditions. Cytotoxicity study showed that the DOX loaded nanogels have significantly enhanced cytotoxicity in vitro compared with the nonsensitive ones. Confocal microscopy revealed that there was more DOX in the nuclei of tumor cells when incubated with DOX-loaded pH sensitive nanogels for 3 to 12 h. The enhanced anticancer activity of DOX-loaded pH-sensitive nanogels was also verified by in vivo therapeutic study on mice, in which tumor volume evolution was measured and tumor tissues cell apoptosis and proliferation was examined.
一种基于天然多糖的纳米凝胶已被合成并表征为用于水溶性差的抗癌药物的pH敏感药物递送系统。在这项工作中，甲基丙烯酸化透明质酸（MAHA）用于通过无表面活性剂聚合方法在水中制备酸可降解纳米凝胶，其中2,2-二甲基丙烯酰氧基-1-乙氧基丙烷（DMAEP）用作pH不稳定交联剂。制备了不同交联密度的纳米凝胶，并将阿霉素（DOX）成功封装到纳米凝胶中，载药量（DLC）范围为7.67%至12.15%。在酸性条件下发现阿霉素加速释放。细胞毒性研究表明，与非敏感纳米凝胶相比，载有阿霉素的纳米凝胶在体外具有显著增强的细胞毒性。共聚焦显微镜显示，当与载有阿霉素的pH敏感纳米凝胶孵育3至12小时时，肿瘤细胞核中有更多的阿霉素。载有阿霉素的pH敏感纳米凝胶增强的抗癌活性也通过对小鼠的体内治疗研究得到验证，其中测量了肿瘤体积变化，并检查了肿瘤组织细胞凋亡和增殖情况。
