广东工业大学学报 ›› 2021, Vol. 38 ›› Issue (01): 89-96.doi: 10.12052/gdutxb.200132

• 综合研究 • 上一篇    下一篇

pH响应型星状聚合物胶束的制备及释药性能

温伟球, 郭建维   

  1. 广东工业大学 轻工化工学院，广东 广州 510006
  • 收稿日期:2020-09-29 出版日期:2021-01-25 发布日期:2020-12-21
  • 通信作者: 郭建维(1968-)，男，教授，主要研究方向为功能高分子聚合物的制备及应用，E-mail：guojw@gdut.edu.cn E-mail:guojw@gdut.edu.cn
  • 作者简介:温伟球(1992-)，男，博士研究生，主要研究方向为刺激响应型聚合物胶束的制备及应用
  • 基金资助:
    广州市科技计划项目(201704030075)

Synthesis of pH-Responsive Star-Shaped Polymeric Micelles for Controlled Drug Delivery

Wen Wei-qiu, Guo Jian-wei   

  1. School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China
  • Received:2020-09-29 Online:2021-01-25 Published:2020-12-21

HTML

PDF (PC)

2751

摘要： 以金刚烷为核设计合成了一种具有pH响应功能的四臂星状聚合物金刚烷-[聚(乳酸-共-羟基乙酸)-聚甲基丙烯酸二乙氨基乙酯-聚(乙二醇)单甲醚]4(4sAd-PLGA-D-P), 制备了4sAd-PLGA-D-P自组装胶束, 考察了该胶束对抗癌药物阿霉素(Doxorubicin，DOX)的控释性能。结果表明: 改变聚甲基丙烯酸二乙氨基乙酯(PDEAEMA)的链段长度可实现对聚合物胶束性能的调控。PDEAEMA链段越长, 聚合物胶束的粒径越大, 载药量越高, 药物累计释放量越高。聚合物胶束具有良好的稳定性(临界胶束浓度(Critical Micelle Concentration，CMC)为0.0031 mg/mL)、pH响应性能和载药能力(载药量高达24.8%)。载DOX胶束在肿瘤微环境pH值(pH=5.0)的累计释放量(85.2%)明显高于正常组织pH=7.4条件下的累计释放量(20.9%), 可实现抗癌药物的可控释放。因此, pH响应型聚合物胶束4sAd-PLGA-D-P在抗癌药物递送领域具有潜在的应用前景。

关键词: pH响应聚合物, 聚合物胶束, 药物递送, 金刚烷

Abstract: A four arm star-shaped pH responsive polymer adamantane-[poly(lactic-co-glycolic acid)-b-poly(N, N'-diethylaminoethyl methacrylate)-poly(ethylene glycol) monomethyl ether]4 was synthesized using adamantane as core. Self-assembly micelles of the synthesized polymer were prepared and the controlled release properties were further investigated. The results showed that the proportion of PDEAEMA had important effects on the properties of polymeric micelles, reflected by the fact that polymeric micelles with longer PDEAEMA segment had larger particle size, better drug loading capacity and higher cumulative drug release. Furthermore, the polymeric micelles had desired stability (CMC 0.0031 mg/mL), good pH-responsive function and high drug loading capacity (up to 24.8%). Under the simulated environment of tumor tissue (pH=5.0), the cumulative release of DOX-loaded micelles (85.2%) was significantly higher than those under the simulated environment of normal tissue (pH=7.4, 20.9%), indicative of the well-controlled release behavior of drug-loaded micelles. In conclusion, such pH-responsive polymeric micelles 4sAd-PLGA-D-P present great potential in the field of anticancer drug delivery.

Key words: pH-responsive polymer, polymeric micelles, drug delivery, adamantane

中图分类号: 

  • TQ317.4
[1] SHI J, KANTOFF P W, WOOSTER R, et al. Cancer nanomedicine: progress, challenges and opportunities [J]. Nature Reviews Cancer, 2017, 17: 20-37.
[2] WICKI A, WITZIGMANN D, BALASUBRAMANIAN V, et al. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications [J]. Journal of Control Release, 2015, 200: 138-57.
[3] LI Y, LU H, LIANG S, et al. Dual stable nanomedicines prepared by cisplatin-crosslinked camptothecin prodrug micelles for effective drug delivery [J]. ACS Applied Materials & Interfaces, 2019, 11(23): 20649-20659.
[4] CHEN Z, LIU W, ZHAO L, et al. Acid-labile degradation of injectable fiber fragments to release bioreducible micelles for targeted cancer therapy [J]. Biomacromolecules, 2018, 19: 1100-1110.
[5] 羊惠燕, 郭建维. 星状pH响应聚合物及其自组装胶束研究[J]. 广东工业大学学报, 2019, 36(1): 81-86.
YANG H Y, GUO J W. A study of star pH-responsive polymer and its self-assembled micelles [J]. Journal of Guangdong University of Technology, 2019, 36(1): 81-86.
[6] FENG J J, WEN W Q, JIA Y G, et al. pH-responsive micelles assembled by three-armed degradable block copolymers with a cholic acid core for drug controlled-release [J]. Polymers, 2019, 11(3): 511.
[7] SONG X, WEN Y T, ZHU J L, et al. Thermoresponsive delivery of paclitaxel by β-cyclodextrin-based poly(N-isopropylacrylamide) star polymer via inclusion complexation [J]. Biomacromolecules, 2016, 12: 2957-3963.
[8] SONG X, ZHU J L, WEN Y T, et al. Thermoresponsive supramolecular micellar drug delivery system based on star-linear pseudo-block polymer consisting of β-cyclodextrin-poly (N-isopropylacrylamide) and adamantyl-poly(ethylene glycol) [J]. Journal of Colloid and Interface Science, 2017, 490: 372-379.
[9] SHI X, HOU M, MA X, et al. Starburst diblock polyprodrugs: reduction-responsive unimolecular micelles with high drug loading and robust micellar stability for programmed delivery of anticancer drugs [J]. Biomacromolecules, 2019, 20: 1190-1202.
[10] LI M, GUO J W, WEN W Q, et al. Biodegradable redox-sensitive star polymer nanomicelles for enhancing doxorubicin delivery [J]. Nanomaterials, 2019, 9(4): 547.
[11] QU J, PENG S, WANG R, et al. Stepwise pH-sensitive and biodegradable polypeptide hybrid micelles for enhanced cellular internalization and efficient nuclear drug delivery [J]. Colloids and Surfaces B Biointerfaces, 2019, 181: 315-324.
[12] XU Z, XUE P, GAO Y E, et al. pH-responsive polymeric micelles based on poly (ethyleneglycol)-b-poly(2-(diisopropylamino) ethyl methacrylate) block copolymer for enhanced intracellular release of anticancer drugs [J]. Journal of Colloid and Interface Science, 2017, 490: 511-519.
[13] LIN W J, YAO N, QIAN L, et al. pH-responsive unimolecular micelle-gold nanoparticles-drug nanohybrid system for cancer theranostics [J]. Acta Biomaterialia, 2017, 58: 455-465.
[14] GUO X, SHI C L, YANG G. Dual-responsive polymer micelles for target-cell-specific anticancer drug delivery [J]. Chemistry of Materials, 2014, 26: 4405-4418.
[15] MAO J, YANG L, WU T, et al. A simple dual-pH responsive prodrug-based polymeric micelles for drug delivery [J]. ACS Applied Materials & Interfaces, 2016, 8: 17109-17117.
[16] ENGLERT J C, BRENDEL T C, MAJDANSKI T, et al. Pharmapolymers in the 21st century: synthetic polymers in drug delivery applications [J]. Progress in Polymer Science, 2018, 87: 107-164.
[17] WANG G, ZHANG L. Synthesis, self-assembly and pH sensitivity of PDEAEMA–PEG–PDEAEMA triblock copolymer micelles for drug delivery [J]. Reactive & Functional Polymers, 2016, 107: 1-10.
[18] YANG C F, XIAO J Y, XIAO W, et al. Fabrication of PDEAEMA-based pH-responsive mixed micelles for application in controlled doxorubicin release [J]. RSC Advances, 2017, 7(44): 27564-27573.
[19] YU L, XIE M, LI Z, et al. Facile construction of near-monodisperse and dual responsive polycarbonate mixed micelles with the ability of pH-induced charge reversal for intracellular delivery of antitumor drugs [J]. Journal of Materials Chemistry B, 2016, 4: 6081-6093.
[20] 冯静洁. 基于胆酸的两亲嵌段聚合物及其作为pH响应药物递送体系的研究[D]. 广州: 广东工业大学, 2019.
[21] XIONG X B, BINKHATHLAN Z, MOLAVI O, et al. Amphiphilic block co-polymers: Preparation and application in nanodrug and gene delivery [J]. Acta Biomaterialia, 2012, 8(6): 2017-2033.
[22] KOBAYASHI H, WATANABE R, CHOYKE P L. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? [J]. Theranostics, 2013, 4(1): 81-89.
[23] LIN W J, NIE S, ZHONG Q, et al. Amphiphilic miktoarm star copolymer (PCL)3-(PDEAEMA-b-PPEGMA)3 as pH-sensitive micelles in the delivery of anticancer drug [J]. Journal of Material Chemistry B, 2014, 2(25): 4008-4020.
[24] SHANG Y Q, ZHENG N, WANG Z G. Tetraphenylsilane-cored star-shaped polymer micelles with pH/redox dual response and active targeting function for drug-controlled release [J]. Biomacromolecules, 2019, 20(12): 4602-4610.
[1] 柳滢春, 郭建维, 罗涛, 吴彤彪. （乙烯基咔唑-对金刚烷基苯乙烯）共聚物的合成与光致发光性能[J]. 广东工业大学学报, 2018, 35(01): 73-76.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2017 《广东工业大学学报》编辑部
地址：广州市东风东路729号广东工业大学 邮编：510090
电话：020-37626653,020-37626139,020-37626396
邮箱：xbzrb@gdut.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发