Preparation of reversible cross-linked amphiphilic polymeric micelles with pH-responsive behavior for smart drug delivery

Liu Tan; Jinling Fan; Yuqing Zhou; Di Xiong; Manzhen Duan; Ding Hu; Zhimin Wu

doi:10.1039/d3ra05575b

Preparation of reversible cross-linked amphiphilic polymeric micelles with pH-responsive behavior for smart drug delivery

RSC Adv. 2023 Sep 25;13(40):28165-28178. doi: 10.1039/d3ra05575b. eCollection 2023 Sep 18.

Authors

Liu Tan^{1

2}, Jinling Fan¹, Yuqing Zhou¹, Di Xiong³, Manzhen Duan¹, Ding Hu^{1

2}, Zhimin Wu^{1

2}

Affiliations

¹ School of Chemical Engineering, Xiangtan University Xiangtan 411105 China huding@hnu.edu.cn xdwuzm@xtu.edu.cn.
² National & Local United Engineering Research Centre for Chemical Process Simulation and Integration, Xiangtan University Xiangtan 411105 China.
³ School of Mechanical & Automotive Engineering, South China University of Technology Guangzhou 510640 China.

Abstract

A new type of reversible cross-linked and pH-responsive polymeric micelle (PM), poly[polyethylene glycol methacrylate-co-2-(acetoacetoxy)ethyl methacrylate]-b-poly [2-(dimethylamino)ethyl methacrylate] [P(PEGMA-co-AEMA)-b-PDMAEMA], was synthesized for targeted delivery of curcumin. After reversible cross-linking of the micellar shell, the PMs with a typical core-shell structure exhibited excellent stability against extensive dilution and good reversibility of pH-responsiveness in solutions with different pH values. P(PEGMA₉-co-AEMA₆)-b-PDMAEMA₁₀ has the lowest critical micelle concentration (CMC) value (0.0041 mg mL^-1), the highest loading capacity (13.86%) and entrapment efficiency (97.03%). A slow sustained drug release at pH 7.4 with 12.36% in 108 h, while a fast release (42.36%) was observed at pH 5.0. Furthermore, a dissipative particle dynamics (DPD) simulation method was employed to investigate the self-assembly process and pH-responsive behavior of PMs. The optimal drug-carrier ratio (2%) and fraction of water (92%) were confirmed by analyzing the drug distribution and morphology of micelles during the self-assembly process of the block copolymer. The simulation results were consistent with experimental results, indicating DPD simulation shows potential to study the structure properties of reversible cross-linked micelles. The present findings provide a new method for the development of SDDS with good structural stability and controlled drug release properties.