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Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties

[Image: see text] Dithiolanes are used to obtain dynamic and reversible crosslinks between polymer chains. Copolymers of two different dithiolane-containing cyclic carbonate monomers and ε-caprolactone (CL) were synthesized by ring-opening polymerization using a methoxy-poly(ethylene glycol) (mPEG)...

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Autores principales: Liu, Yanna, van Steenbergen, Mies J., Zhong, Zhiyuan, Oliveira, Sabrina, Hennink, Wim E., van Nostrum, Cornelus F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458473/
https://www.ncbi.nlm.nih.gov/pubmed/32884159
http://dx.doi.org/10.1021/acs.macromol.0c01031
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author Liu, Yanna
van Steenbergen, Mies J.
Zhong, Zhiyuan
Oliveira, Sabrina
Hennink, Wim E.
van Nostrum, Cornelus F.
author_facet Liu, Yanna
van Steenbergen, Mies J.
Zhong, Zhiyuan
Oliveira, Sabrina
Hennink, Wim E.
van Nostrum, Cornelus F.
author_sort Liu, Yanna
collection PubMed
description [Image: see text] Dithiolanes are used to obtain dynamic and reversible crosslinks between polymer chains. Copolymers of two different dithiolane-containing cyclic carbonate monomers and ε-caprolactone (CL) were synthesized by ring-opening polymerization using a methoxy-poly(ethylene glycol) (mPEG) initiator and different catalysts (diphenyl phosphate (DPP), methanesulfonic acid (MSA), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), or Sn(Oct)(2)). Each catalyst required a different temperature, which had a pronounced influence on the reactivity ratio of the monomers and occurrence of transesterification reactions and, therefore, the monomer sequence. Self-crosslinkable copolymers were obtained when the dithiolane units were connected closely to the polymer backbone, whereas the presence of a linker unit between the dithiolane and the backbone prevented self-crosslinking. The former amphiphilic PEGylated block copolymers formed micelles by nanoprecipitation in the aqueous environment and crosslinked spontaneously by disulfide exchange during subsequent dialysis. These dithiolane-crosslinked micelles showed reduction-responsive dissociation in the presence of 10 mM glutathione, making them promising drug delivery systems for the intracellularly triggered cargo release.
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spelling pubmed-74584732020-09-01 Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties Liu, Yanna van Steenbergen, Mies J. Zhong, Zhiyuan Oliveira, Sabrina Hennink, Wim E. van Nostrum, Cornelus F. Macromolecules [Image: see text] Dithiolanes are used to obtain dynamic and reversible crosslinks between polymer chains. Copolymers of two different dithiolane-containing cyclic carbonate monomers and ε-caprolactone (CL) were synthesized by ring-opening polymerization using a methoxy-poly(ethylene glycol) (mPEG) initiator and different catalysts (diphenyl phosphate (DPP), methanesulfonic acid (MSA), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), or Sn(Oct)(2)). Each catalyst required a different temperature, which had a pronounced influence on the reactivity ratio of the monomers and occurrence of transesterification reactions and, therefore, the monomer sequence. Self-crosslinkable copolymers were obtained when the dithiolane units were connected closely to the polymer backbone, whereas the presence of a linker unit between the dithiolane and the backbone prevented self-crosslinking. The former amphiphilic PEGylated block copolymers formed micelles by nanoprecipitation in the aqueous environment and crosslinked spontaneously by disulfide exchange during subsequent dialysis. These dithiolane-crosslinked micelles showed reduction-responsive dissociation in the presence of 10 mM glutathione, making them promising drug delivery systems for the intracellularly triggered cargo release. American Chemical Society 2020-08-03 2020-08-25 /pmc/articles/PMC7458473/ /pubmed/32884159 http://dx.doi.org/10.1021/acs.macromol.0c01031 Text en Copyright © 2020 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Liu, Yanna
van Steenbergen, Mies J.
Zhong, Zhiyuan
Oliveira, Sabrina
Hennink, Wim E.
van Nostrum, Cornelus F.
Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties
title Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties
title_full Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties
title_fullStr Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties
title_full_unstemmed Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties
title_short Dithiolane-Crosslinked Poly(ε-caprolactone)-Based Micelles: Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties
title_sort dithiolane-crosslinked poly(ε-caprolactone)-based micelles: impact of monomer sequence, nature of monomer, and reducing agent on the dynamic crosslinking properties
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458473/
https://www.ncbi.nlm.nih.gov/pubmed/32884159
http://dx.doi.org/10.1021/acs.macromol.0c01031
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