离子液体中ATRP合成MCC-g-PMAA及其分子对阿司匹林控释的应用

doi:10.11949/j.issn.0438-1157.20161122

化工学报 ›› 2016, Vol. 67 ›› Issue (S2): 164-170.DOI: 10.11949/j.issn.0438-1157.20161122

• 催化、动力学与反应器 • 上一篇下一篇

离子液体中ATRP合成MCC-g-PMAA及其分子对阿司匹林控释的应用

杜煌, 常达, 唐二军, 袁淼, 刘少杰

河北科技大学化学与制药工程学院, 河北省药物化工工程技术中心, 河北石家庄 050018

收稿日期:2016-08-08 修回日期:2016-10-10 出版日期:2016-12-30 发布日期:2016-12-30
通讯作者: 唐二军
基金资助:
河北省自然科学基金项目（B2013208183）；河北省教育厅重点项目（ZD2014086）。

Synthesis of MCC-g-PMAA by ATRP in ILs and its application in controlled release to Aspirin

DU Huang, CHANG Da, TANG Erjun, YUAN Miao, LIU Shaojie

Hebei Research Center of Pharmaceutical and Chemical Engineering, Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, Hebei, China

Received:2016-08-08 Revised:2016-10-10 Online:2016-12-30 Published:2016-12-30
Supported by:
supported by the Natural Science Foundation of Hebei Province (B2013208183)and the State Key Program from Ministry of Education of Hebei Province (ZD2014086).

摘要/Abstract

摘要：

以离子液体氯化1-烯丙基-3-甲基咪唑（[Amim]Cl）为反应介质，利用原子转移自由基聚合（atom transfer radical polymerization，ATRP）法合成了微晶纤维素接枝有聚甲基丙烯酸（MCC-g-PMAA）的pH敏感性聚合物。用透析法将模型药物阿司匹林包覆在聚合物胶束内，并对载药胶束的体外药物释放机制进行研究。通过红外、核磁、透射电镜、X射线衍射和紫外分光光度计等分析手段对聚合物的结构、胶束形貌、胶束对阿司匹林的载药性能及释药性能进行了表征分析。结果表明：聚合物胶束能够在水溶液中自组装成球状胶束，对阿司匹林具有良好的包载效果，阿司匹林在碱性条件下的累积释放量大于酸性条件，载药胶束表现出了良好的pH敏感性和药物缓释性能。

关键词: 离子液体, ATRP, 透析, 载药胶束, 水溶液, pH敏感性

Abstract:

Ionic liquid 1-allyl-3-methyl-imidazole chloride ([Amim]Cl) as reaction medium,the microcrystalline cellulose graft poly methylacrylic acid (MCC-g-P4VP) polymer with pH-sensitivity were synthesized by atom transfer radical polymerization (ATRP).The model drug Aspirin was entrapped in polymeric micelles by dialysis method.The release mechanism of drug loaded micelle in vitro was analyzed.The polymer structure,micellar morphology,performance of aspirin loading and drug releasing were characterized by means of FT-IR,¹H NMR,TEM,XRD and UV-Vis.The results showed that the micelle could form spherical morphology micelles by self-assembly in aqueous solution, it presented a perfect encapsulation about Aspirin.It was found that the cumulant release of Aspirin in basic environment was higher than that in acidic environment.The drug loaded micelle showed excellent properties of pH-sensitivity and drug sustained-release.

Key words: ionic liquid, ATRP, dialysis, drug loaded micelle, aqueous solution, pH-sensitivity

中图分类号:

TQ469

杜煌, 常达, 唐二军, 袁淼, 刘少杰. 离子液体中ATRP合成MCC-g-PMAA及其分子对阿司匹林控释的应用[J]. 化工学报, 2016, 67(S2): 164-170.

DU Huang, CHANG Da, TANG Erjun, YUAN Miao, LIU Shaojie. Synthesis of MCC-g-PMAA by ATRP in ILs and its application in controlled release to Aspirin[J]. CIESC Journal, 2016, 67(S2): 164-170.

参考文献 22

[1]	周雪,薛雨晨,贺智勇,等.阿司匹林PEG-PLGA缓释微球的制备以及体外释药的考察[J]. 中国医院药学杂志,2014,34(22):1889-1893. ZHOU X,XUE Y C,HE Z Y,et al.Study on the preparation and in vitro release characterization of Aspirin PEG-PLGA sustained release microspheres[J]. Chinese Journal of Hospital Pharmacy,2014,34(22):1889-1893.
[2]	曾春香,张斯汉.缓释、控释药用高分子材料的临床应用[J]. 中国组织工程研究,2010,14(21):3939-3942. ZENG C X,ZHANG S H.Clinical application of sustained-release and controlled-release medical polymer materials[J]. Chinese Journal of Tissue Engineering Research,2010,14(21):3939-3942.
[3]	张广志,孙晨雅,蒋学,等.超声-微波共辐射法合成纤维素-MMA接枝共聚物[J]. 化工学报,2012,63(8):2661-2666. ZHANG G Z,SUN C Y,JIANG X, et al.Synthetic MCC-MMA graft copolymer under ultrasound-microwave collaborative irradiation[J]. CIESC Journal,2012,63(8):2661-2666.
[4]	叶代勇,黄洪,傅和青,等.纤维素化学研究进展[J]. 化工学报,2006,57(8):1782-1791. YE D Y,HUANG H,FU H Q, et al.Advances in cellulose chemistry[J]. Journal of Chemical Industry and Engineering(China),2006,57(8):1782-1791.
[5]	袁丽.刺激响应性纳米药物控释系统的制备及应用研究[D]. 上海:复旦大学,2013. YUAN L.Preparation of stimuli-responsive nanomaterials and their application in controlled drug delivery[D]. Shanghai:Fudan University,2013.
[6]	尹婵,魏晓奕,李积华,等.天然植物纤维素的改性技术及研究进展[J]. 广东化工,2012,39(15):17-19. YIN C,WEI X Y,LI J H,et al.The research progress of cellulose modification technology[J]. Guangdong Chemical Industry,2012,39(15):17-19.
[7]	MATYJASZEWSKI K,GAYNOR S,WANG J S.Controlled radical polymerizations:the use of alkyl iodides in degenerative transfer[J]. Macromolecules,1995,28(6):2093-2095.
[8]	哈丽丹·买买提,开比努尔·艾尔肯,米娜瓦尔·乌买尔. ATRP法均相制备纤维素/甲基丙烯酸丁酯接枝聚合物[J]. 化工学报,2014,65(3):1111-1117. HALIDAN M,KAIBINUR A,MINAWAR W.Preparation of cellulose graft poly(butyl methacrylate)copolymers by homogeneous ATRP[J]. CIESC Journal,2014,65(3):1111-1117.
[9]	ZAMPANO G,BERTOLDO M,BRONCO S.Poly(ethyl acrylate)surface-initiated ATRP grafting from wood pulp cellulouse fibers[J]. Catbohyd.Polym.,2009,75:22-31.
[10]	TANG E J,TIAN B Y,ZHAO D S,et al.Effect of different ligands on the controlled polymerization of monodisperse polystyrene nanospheres by ATRP[J]. Express Polym.Lett.,2012,6(10):837-846.
[11]	杜凯迪,唐二军,袁淼,等.[AMIM]Cl离子液体中纤维素接枝PDEAEMA分子刷的均相可控聚合[J]. 化工学报,2015,66(11):4275-4280. DU K D,TANG E J,YUAN M, et al.Controlled synthesis of cellulose grafting PDEAEMA brushes by ATRP in ionic liquid[AMIM]Cl[J]. CIESC Journal,2015,66(11):4275-4280.
[12]	LUO Y L,YANG X L,XU F, et al.pH-triggered PMAA-b-HTPB-b-PMAA copolymer micelles:physicochemical charac-terization and camptothec in release[J]. Colloid Polym.Sci.,2014,292(5):1061-1072.
[13]	张晓君,刘辉,胡海洋,等.聚合物胶束作为药物传递系统的研究进展[J]. 沈阳药科大学学报,2014,31(8):589-590. ZHANG X J,LIU H,HU H Y, et al.Preparation and in vitro evaluation of paclitaxel-loaded copolymeric micelles[J]. Journal of Shenyang Pharmaceutical University,2014,31(8):589-590.
[14]	刘真真.两亲性嵌段共聚物的合成及其敏感行为研究[D]. 合肥:安徽大学,2013. LIU Z Z.Synthesis and pH-sensitive behavior of amphiphilic block copolymers[D]. Hefei:Anhui University,2013.
[15]	钟黎黎,高源,张力平.cellulose-g-PMMA的合成及其胶束作为药物载体的研究[J]. 林产化学与工业,2015,35(1):23-29. ZHONG L L,GAO Y,ZHANG L P.Synthesis of cellulose-g-PMMA and its micelles using as drug carriers[J]. Chemistry and Industry of Forest Products,2015,35(1):23-29.
[16]	郭延柱.两亲性纤维素及其自组装纳米胶束的制备与应用研究[D]. 广州:华南理工大学,2013. GUO Y Z.Study on the preparation and application of amphiphilc cellulose copolymers and their self-assembled nanomicelles[D]. Guangzhou:South China University of Technology,2013.
[17]	WANG D Q,TAN J J,KANG H L,et al.Synthesis,self-assembly and drug release behaviors of pH-responsive copolymers ethyl cellulose-graft-PDEAEMA through ATRP[J]. Carbohydrate Polymers,2011,84(1):195-202.
[18]	谭清华,杨江静,唐艳辉,等.青蒿素-β-环糊精包合物的制备及表征[J]. 吉首大学学报,2013,34(4):72-76. TAN Q H,YANG J J,TANG Y H,et al.Preparation and characterization of inclusion complex arteannuin with β-cyclodextrin[J]. Journal of Jishou University,2013,34(4):72-76.
[19]	LUO Y,LI L,WANG Y,et al.Preparation and characteristic of hydroxycamptothecin-loaded PLA nanoparticles using dialysis method[J]. J.Xiamen University Nat.Sci.,2010,49(6):832-837.
[20]	YAO R,LIU L,DENG S,et al.Preparation of carboxymeth-ylchitosan nanoparticles with acid-sensitive bond based on solid dispersion of 10-hydroxycamptothecin[J]. ISRN Pharmaceutics,2011,2011:1-9.
[21]	杨友强.pH响应聚合物及其胶束给药系统:制备和结构性能关系[D]. 广州:华南理工大学,2012. YANG Y Q.Preparation and structure-performance relationship of pH-sensitive polymers and their self-assembled micelle drug delivery system[D]. Guangzhou:South China University of Technology,2012.
[22]	RANJHA N M,AYUB G,NASEEM S,et al.Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil[J]. J. Mater. Sci.Mater.Med.,2010,21(10):2805-2816.

离子液体中ATRP合成MCC-g-PMAA及其分子对阿司匹林控释的应用

Synthesis of MCC-g-PMAA by ATRP in ILs and its application in controlled release to Aspirin

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