Controlling Membrane Phase Separation of Polymersomes for Programmed Drug Release

Shuai Chen; Erik Jan Cornel; Jian-Zhong Du

doi:10.1007/s10118-022-2683-7

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Controlling Membrane Phase Separation of Polymersomes for Programmed Drug Release

RESEARCH ARTICLE | Updated：2022-08-19

- Controlling Membrane Phase Separation of Polymersomes for Programmed Drug Release
  Enhanced Publication
- Chinese Journal of Polymer Science Vol. 40, Issue 9, Pages: 1006-1015(2022)
- Affiliations：
  
  a.Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
  b.Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
- Author bio：
  
  jzdu@tongji.edu.cn
- Funds：
- DOI：10.1007/s10118-022-2683-7
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Shuai Chen, Erik Jan Cornel, Jian-Zhong Du. Controlling Membrane Phase Separation of Polymersomes for Programmed Drug Release. [J]. Chinese Journal of Polymer Science 40(9):1006-1015(2022)
DOI：

Shuai Chen, Erik Jan Cornel, Jian-Zhong Du. Controlling Membrane Phase Separation of Polymersomes for Programmed Drug Release. [J]. Chinese Journal of Polymer Science 40(9):1006-1015(2022) DOI： 10.1007/s10118-022-2683-7.

摘要

We proposed a new strategy to control the drug release rate of polymersomes by controlling membrane phase separation. This was achieved by employing membrane-forming blocks with different molecular architectures and cross-linking degrees. This work shed light on the design of programmed drug release vehicles.

Abstract

Programmed release of small molecular drugs from polymersomes is of great importance in drug delivery. A significant challenge is to adjust the membrane permeability in a well-controlled manner. Herein, we propose a strategy for controlling membrane phase separation by photo-cross-linking of the membrane-forming blocks with different molecular architectures. We synthesized three amphiphilic block copolymers with different membrane-forming blocks, which are poly(ethylene oxide),43,-,b,-poly((,ε,-caprolactone),45,-,stat,-((,α,-(cinnamoyloxymethyl)-1,2,3-triazol)caprolactone),25,) (PEO,43,-,b,-P(CL,45,-,stat,-CTCL,25,)), PEO,43,-,b,-P(CL,108,-,stat,-CTCL,16,), and PEO,43,-,b,-PCTCL,4,-,b,-PCL,79,. These polymers were self-assembled into polymersomes using either a solvent-switch or powder rehydration method, and the obtained polymersomes were characterized by dynamic light scattering and transmission electron microscopy. Then the phase separation patterns within the polymersome membranes were investigated by mesoscopic dynamics (MesoDyn) simulations. To further confirm the change of the membrane permeability that resulted from the phase separation within the membrane, doxorubicin, as a small molecular drug, was loaded and released from the polymersomes. Due to the incompatibility between membrane-forming moieties (PCTCL and PCL), phase separation occurs and the release rate can be tuned by controlling the membrane phase pattern or by photo-cross-linking. Moreover, besides the compacting effect by formation of chemical bonds in the membrane, the cross-linking process can act as a driving force to facilitate the rearrangement and re-orientation of the phase pattern, which also influences the drug release behavior by modulating the cross-membrane distribution of the amorphous PCTCL moieties. In this way, the strategy of focusing on the membrane phase separation for the preparation of the polymersomes with finely tunable drug release rate can be envisioned and designed accordingly, which is of great significance in the field of delivery vehicles for programmed drug release.

关键词

Keywords

PolymersomeDrug deliveryPhase separationProgrammed drug release

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