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pH sensitive polymeric complex of cisplatin with hyaluronic acid exhibits tumor-targeted delivery and improved in vivo antitumor effect 期刊论文

编号：

d40134f7-5630-46cd-a6f0-4a8f53143d42
作者：

Fan, Xiaohong(范小红)#*^[1]Zhao, Xuesong(赵雪松)#^[2]Qu, Xinkai^[3];Fang, Jun(方军)*^[4]
语种：

英文
期刊：

INTERNATIONAL JOURNAL OF PHARMACEUTICS ISSN：0378-5173 2015 年 496 卷 2 期 (644 - 653) ; DEC 30
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关键词：

EPR effect Tumor targeting Antitumor therapy Hyaluronic acid Cisplatin
摘要：

Cisplatin (CDDP) is widely used anticancer drug for various solid tumors including lung cancer. However, its indiscriminate distribution causes serious adverse effects and limits its therapeutic effect. In this study, by using hyaluronic acid (HA) we synthesized a complex of CDDP (HA-CDDP), by utilizing ionic interaction between Pt2+ of CDDP with carboxyl group of HA. The mean HA-CDDP particle size was 208.5 nm in PBS according to dynamic light scattering which was also confirmed by TEM, which could exert tumor-targeting property by enhanced permeability and retention (EPR) effect. The CDDP loading in this preparation was 13% (w/w), and release rate of free CDDP from the HA-CDDP complex at physiological pH (7.4) was similar to 20%/day. However, in acidic pH the release was much faster, i.e., similar to 95% of CDDP was released in 72 h at pH 5.5. Moreover, HA-CDDP showed a 2.5-fold higher tumor accumulation than free CDDP whereas no increase of distribution was found in most normal tissues. In addition, because HA receptor CD44 is overexpressed in many tumor cells, we also observed CD44-based endocytosis of HA-CDDP in mouse lung carcinoma LCC cells. These findings together suggest that HA-CDDP may show tumor-selective cytotoxicity by taking advantage of EPR effect, weak acidic environment of tumor tissues (e. g., pH 6 similar to 7), as well as CD44-based intracellular uptake. As expected, HA-CDDP exhibited much improved therapeutic effect than free CDDP in mouse LCC tumor model, whereas no apparent side effect was found. These findings may shed some light on the potential utility of HA for development of tumor-targeted polymeric CDDP drugs, which need further investigations. (C) 2015 Elsevier B.V. All rights reserved.
推荐引用方式
GB/T 7714：

Fan Xiaohong,Zhao Xuesong,Qu Xinkai, et al. pH sensitive polymeric complex of cisplatin with hyaluronic acid exhibits tumor-targeted delivery and improved in vivo antitumor effect [J].INTERNATIONAL JOURNAL OF PHARMACEUTICS,2015,496(2):644-653.
APA：

Fan Xiaohong,Zhao Xuesong,Qu Xinkai,Fang Jun.(2015).pH sensitive polymeric complex of cisplatin with hyaluronic acid exhibits tumor-targeted delivery and improved in vivo antitumor effect .INTERNATIONAL JOURNAL OF PHARMACEUTICS,496(2):644-653.
MLA：

Fan Xiaohong, et al. "pH sensitive polymeric complex of cisplatin with hyaluronic acid exhibits tumor-targeted delivery and improved in vivo antitumor effect" .INTERNATIONAL JOURNAL OF PHARMACEUTICS 496,2(2015):644-653.
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