pH-响应型K5多糖药物传递系统的构建及应用

doi:10.16085/j.issn.1000-6613.2016.s2.053

化工进展 ›› 2016, Vol. 35 ›› Issue (S2): 305-310.DOI: 10.16085/j.issn.1000-6613.2016.s2.053

pH-响应型K5多糖药物传递系统的构建及应用

叶宝彤, 宋家鸿, 彭换换, 陈荆晓, 陈敬华

江南大学药学院, 江苏无锡 214122

收稿日期:2016-09-26 出版日期:2016-12-31 发布日期:2016-12-22
通讯作者: 陈敬华,教授,主要研究方向为生物制药与生物活性大分子。E-mail:jhchenwhut@126.com。
作者简介:叶宝彤(1994-),男,硕士研究生,主要研究方向为纳米药物传递系统。
基金资助:
国家自然科学基金项目（51303068，21574059，21306066）。

Construction and application of novel pH responsive drug delivery system based on K5 polysaccharide

YE Baotong, SONG Jiahong, PENG Huanhuan, CHEN Jingxiao, CHEN Jinghua

School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, Jiangsu, China

Received:2016-09-26 Online:2016-12-31 Published:2016-12-22

摘要/Abstract

摘要： 化学疗法是目前癌症治疗的主要方法，但目前常用的化疗药物却普遍存在水溶性不佳、缺乏选择性、毒副作用大等不足，而限制了其应用。本研究基于肝素前体K5多糖为模板，利用具有pH响应性的硼酸酯键，构建了K5-脱氧胆酸（K5AD）两亲性药物传递系统，用于阿霉素（doxorubicin，DOX）的靶向传递释放。考察了该体系的体外药物释放行为，并在体外评价其对肿瘤细胞的抑制作用。结果表明，K5AD的临界胶束浓度值为23.5mg/L，在水溶液中能自组装形成平均粒径为196.7nm的胶束；K5AD-DOX体外药物释放实验显示其具有pH-响应的释药行为，在pH 5.0的酸性环境下药物释放速率较pH 7.4下更快。细胞实验表明，K5AD-DOX对肿瘤细胞的毒性远大于对正常细胞的毒性，表现出治疗的选择性。

关键词: K5多糖, 硼酸酯, pH响应, 药物传递系统

Abstract: Chemotherapy is the one of the main methods used for cancer therapy.However,current chemotherapeutics exhibit poor water solubility,low selectivity and strong side-effects,while limiting their applications.In this study,we used the precursor of heparin,K5 polysaccharide,as the building block,which conjugated with deoxycholic acid via boronate ester bond,to construct a novel amphiphilic drug delivery system for the transportation of doxorubicin(DOX).The in vitro drug release behavior and anticancer efficacy of K5AD were evaluated.The results showed that the critical micelle concentration(CMC) of K5AD micelles was 23.5mg/L,and their average particle size was 196.7 nm.In vitro drug release assay indicated the variation of pH value could adjust drug release rate,which was faster at acidic milieu(pH 5.0) than at pH 7.4.The cytotoxicity assay showed that K5AD-DOX could significantly inhibit the proliferation of cancer cells rather than normal cells,showing favorable selectivity during the treatment.

Key words: K5 polysaccharide, boronate ester, pH responsive, drug delivery system

中图分类号:

TQ464

叶宝彤, 宋家鸿, 彭换换, 陈荆晓, 陈敬华. pH-响应型K5多糖药物传递系统的构建及应用[J]. 化工进展, 2016, 35(S2): 305-310.

YE Baotong, SONG Jiahong, PENG Huanhuan, CHEN Jingxiao, CHEN Jinghua. Construction and application of novel pH responsive drug delivery system based on K5 polysaccharide[J]. Chemical Industry and Engineering Progree, 2016, 35(S2): 305-310.

参考文献

[1] STELLA V J,NTI-ADDAE K W.Prodrug strategies to overcome poor water solubility[J].Advanced Drug Delivery Reviews,2007,59(7):677-694.
[2] MAEDA H,BHARATE G Y,DARUWALLA J.Polymeric drugs for efficient tumor-targeted drug delivery basedon EPReffect[J].European Journal of Pharmaceutics and Biopharmaceutics,2009,71(3):409-419.
[3] PANCHAGNULA R.Pharmaceutical aspects of paclitaxel[J].International Journal of Pharmaceutics,1998,172(1):1-15.
[4] SILVA J,FEMANDES A R,BAPTISTA P V.Application of nanotechnology in drug delivery[M].Nanotechnology and Nanomaterials,2014:127-154.
[5] FLEIGE E,QUADIR M A,HAAG R.Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds:concepts and applications[J].Advanced Drug Delivery Reviews,2012,64(9):866-884.
[6] PETROS R A,DESIMONE J M.Strategies in the design of nanoparticles for therapeutic applications[J].Dressnature Reviews Drug Discovery,2010,9(9):615-627.
[7] RAMAN K,MENCIO C,DESAI U R,et al.Sulfation patterns determine cellular internalization of heparin-like polysaccharides[J].Mol.Pharm.,2013,10(4):1442-1449.
[8] DE ANGELIS P L.HEPtune:a process of conjugating a naturally occurring sugar molecule,heparosan,to a drug for enhanced drug delivery[J].Drug Dev.Deliv.,2013,13(1):34-38.
[9] CHEN J X,ZHANG M,LIU W,et al.Construction of serum resistant micelles based on heparosan for targeted cancer therapy[J].Carbohydr.Polym.,2014,110:135-141.
[10] CHEN J X,LIU W,ZHANG M,et al.Heparosan based negatively charged nanocarrier for rapid intracellular drug delivery[J].Int.J.Pharm.,2014,473(1/2):493-500.
[11] LI L,BAI Z,LEVKIN P A.Boronate-dextran:an acid-respo-nsive biodegradable polymer for drug delivery[J].Biomaterials,2013,34(33):8504-8510.
[12] SU J,CHEN F,CRYNS V L,et al.Catechol polymers for pH-responsive,targeted drug delivery to cancer cells[J].J.Am.Chem.Soc.,2011,133(31):11850-11853.
[13] JIA H Z,ZHU J Y,WANG X L,et al.A boronate-linked linear-hyperbranched polymeric nanovehicle for pH-dependent tumor-targeted drug delivery[J].Biomaterials,2014,35(19):5240-5249.

pH-响应型K5多糖药物传递系统的构建及应用

Construction and application of novel pH responsive drug delivery system based on K5 polysaccharide

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 8

编辑推荐

Metrics

本文评价

[1]	王少凡, 周颖, 郝康安, 黄安荣, 张如菊, 吴翀, 左晓玲. 具有pH响应性的自愈合蓝光水凝胶[J]. 化工进展, 2023, 42(9): 4837-4846.
[2]	于丁一, 李圆圆, 王晨钰, 纪永升. pH响应性木质素水凝胶的制备及药物控释[J]. 化工进展, 2023, 42(6): 3138-3146.
[3]	刘慧慧, 史笑飞, 王倩男, 刘锦博, 张静. pH响应性磁性介孔纳米载药系统的制备[J]. 化工进展, 2023, 42(10): 5390-5398.
[4]	李梓泳, 马憬希, 赵明, 陈龙, 周红军, 周新华. 羧甲基纤维素-大豆分离蛋白农药缓释颗粒的制备及性能[J]. 化工进展, 2021, 40(5): 2739-2746.
[5]	孟戎茜, 李巧玲, 晋日亚. TiO₂纳米结构作为载体在药物缓控释传递系统的应用[J]. 化工进展, 2018, 37(10): 3980-3987.
[6]	朱苗, 王鉴, 唐海燕, 孙苒荻, 徐红彬, 张懿. 一种含氮硫杂环硼酸酯的制备及摩擦学性能[J]. 化工进展, 2016, 35(07): 2179-2185.
[7]	褚良银，谢锐，巨晓洁. 智能膜材料研究新进展 [J]. 化工进展, 2011, 30(1): 167-.
[8]	谢钦钦，辛梅华，李明春，毛扬帆. pH响应水溶性荧光标记壳聚糖的制备及表征 [J]. 化工进展, 2010, 29(10): 1943-.