K5多糖-棉酚纳米载体构建及药物传递研究.PDF

第9 卷 第5 期 Vo l.9 No .5 2016 年 3 月 March 2016 K5 多糖-棉酚纳米载体构建及药物传递研究 施 瑜，彭换换，田慧慧，王 睿，徐晓宇，陈敬华* （江南大学药学院，江苏无锡 214122） 摘要：抗前列腺癌药物棉酚（gossypol，GP）水溶性差，治疗选择性不佳，毒副作用大。研究制备了基于硼酸 酯键的 pH 响应型 K5 多糖-GP 缀合物（简记 KGP），考察其自组装和体外药物释放行为，并初步评价其对前 列腺癌细胞的抑制作用。结果表明，KGP 可在水溶液中自组装形成平均粒径为 221.6 nm 的纳米粒子；体外药 物释放实验证实其可表现出受 pH 调控的释药行为，在 pH=5.0 酸性环境下药物释放速率较 pH=7.4 下更快。体 外细胞毒性结果显示其能显著抑制前列腺癌细胞增殖，并且对正常细胞毒性较小，表现出治疗的选择性。细 胞摄取结果表明，异硫氰酸荧光素（fluorescein isothiocyanate，FITC）标记 KGP 可被 PC-3 细胞迅速摄取，且 摄取率高于 COS7 细胞。KGP 纳米载体有望用于治疗前列腺癌。 关键词：药剂学；K5 多糖；棉酚；硼酸酯；前列腺癌 中图分类号：R944.9 文献标识码：A 文章编号：1674-2850(2016)05-0512-06 Construction of K5 polysaccharide-gossypol nanocarrier for drug delivery SHI Yu, PENG Huanhuan, TIAN Huihui, WANG Rui, XU Xiaoyu, CHEN Jinghua (School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, China) Abstract: Gossypol is a chemotherapeutic agent for prostate cancer therapy, but its poor solubility, lack of selectivity and high side-effects limit the application. In this paper, a K5 polysaccharede-gossypol conjugate (KGP) based on boronate ester, which is pH sensitive, was prepared as a drug delivery system. The self-assembly, in vitro drug release behaviors, and anticancer efficacy were evaluated. The results showed that KGP could self-assemble into nanoparticles in water medium with the average size at 221.6 nm. In vitro drug release assay indicated the drug release rate could be adjusted by the variation of pH values. The nanoparticles exhibited faster drug release rate at acidic pH=5.0 than that at pH=7.4. The cytotoxicity assay in vitro illustrated that KGP could significantly inhibit the proliferation of prostate