Preparation and Characterization of Core-cross-linked pH-Responsive Micelles Containing Sulfobetaines

Song-bai Zhang; Lei Huang; Zheng-zhong Wu; Jun Cao; Yuan-wei Chen; Xiang-lin Luo

doi:10.11777/j.issn1000-3304.2017.16247

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Preparation and Characterization of Core-cross-linked pH-Responsive Micelles Containing Sulfobetaines

Research Article | 更新时间：2021-03-19

- Preparation and Characterization of Core-cross-linked pH-Responsive Micelles Containing Sulfobetaines
- Acta Polymerica Sinica Issue 5, Pages: 793-801(2017)
- 作者机构：
  
  1.四川大学高分子科学与工程学院成都 610065
  2.四川大学高分子材料工程国家重点实验室 (四川大学) 成都 610065
  3.四川大学生物材料工程研究中心成都 610065
- 作者简介：
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2017.16247
  CLC：
- Published：2017-5，
  
  Received：3 August 2016，
  
  Revised：14 September 2016，
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Song-bai Zhang, Lei Huang, Zheng-zhong Wu, Jun Cao, Yuan-wei Chen, Xiang-lin Luo. Preparation and Characterization of Core-cross-linked pH-Responsive Micelles Containing Sulfobetaines. [J]. Acta Polymerica Sinica (5):793-801(2017)
DOI：

Song-bai Zhang, Lei Huang, Zheng-zhong Wu, Jun Cao, Yuan-wei Chen, Xiang-lin Luo. Preparation and Characterization of Core-cross-linked pH-Responsive Micelles Containing Sulfobetaines. [J]. Acta Polymerica Sinica (5):793-801(2017) DOI： 10.11777/j.issn1000-3304.2017.16247.

摘要

制备了一种在疏水段带有侧基叠氮官能团的两亲性pH敏感的聚合物--聚己内酯-聚（甲基丙烯酸二乙氨基乙酯-磺酸甜菜碱）（（PCL-ACL）-PDEAS）；同时合成了两端带有炔基中间带有二硫键的交联剂，用红外、核磁表征了目标分子.通过两亲性高分子自组装形成胶束，并通过点击化学反应获得了核交联的胶束.通过动态光散射测定粒径，胶束酸碱滴定表征胶束的pH敏感性，还原条件下释放药物的速度，对比了非交联胶束和交联胶束的性质.结果表明，交联胶束在正常生理条件下的释放速度比未交联胶束更慢；而在有DTT的存在条件下，交联胶束由于二硫键断裂，释放速率明显加快.因此，核交联载药胶束有可能响应肿瘤的微环境实现靶向释放.

Abstract

Polymeric micelles after cross-linking can be overcome dissociation over dilution. In order to obtain cross-linked micelles

a novel pH-responsive copolymer

P (CL-ACL)-PDEAS

namely

poly (

-caprolactone/aazidecaprolactone)-

-poly (

-diethylaminoethylmethacrylate)-

-poly (

-(3-sulfopropyl)-

-methacy-loxyethy-

-diethylammoniumbetaine) was synthesized with azide groups in the hydrophobic block. A cross-linker

2'-bi (2"-acetylene ethyl formate) amide ethyl disulfide

was also synthesized. The synthesis process of P (CL-ACL)-PDEAS included a combination of ring-open polymerization of caprolactone monomers

replacement and transformation of end functional groups

atom transfer radical of DEA monomers and sulfonation of DEA groups. The successful synthesis of the copolymer and the cross-linker were confirmed by nuclear magnetic resonance

Fourier transform infraredand elemental analysis. P (CL-ACL)-PDEAS was used to form polymer micelles by self-assembly. The cross-linked micelles were obtained through "click" chemistry by adding the cross-linker and catalyst during the process of micelle formation. Laser particle size analyzer (DLS) and fluorescence spectrophotometer were used to characterize the properties of the micelles. As a result

the sizes of the uncross-linked micelles and cross-linked micelles were 97.34 and 121.8 nm

respectively

and unimodal size distribution was observed for both types of the micelles. However

after 1000 fold dilution

the size of the cross-linked micelles and their unimodal distribution remained

while the size of the uncross-linked micelles increased greatly and the size distribution became dual. This meant that the cross-linked micelles were more stable. In addition

acid-base titration test showed that both types of the micelles were pH-sensitive. Drug loading and release experiment were carried out using DOX as drug model. The drug loading content and the drug loading efficiency were similar for both types of the micelles. Finally

drug release experiment was executed in different conditions by simulating the human body's physiological environment. The results indicated that the cross-linked micelles released less DOX than the uncross-linked micelles under normal physiological conditions

whereas in the presence of DTT

the release rate of the cross-linked micelles was significantly accelerated

due to the disulfide bond breaking. Thus

as drug delivery carrier

the cross-linked micelles were able to release drug at specific site of tumor in response to the tumor microenvironment.

关键词

交联胶束药物载体点击化学磺酸甜菜碱

Keywords

Cross-linked micellesDrug deliveryClick-chemistrySulfobetaines

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Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences

State Key Laboratory of Polymer Material and Engineering, Sichuan University

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