TY - JOUR
T1 - Dithiolane-Crosslinked Poly(ϵ-caprolactone)-Based Micelles
T2 - Impact of Monomer Sequence, Nature of Monomer, and Reducing Agent on the Dynamic Crosslinking Properties
AU - Liu, Yanna
AU - Van Steenbergen, Mies J.
AU - Zhong, Zhiyuan
AU - Oliveira, Sabrina
AU - Hennink, Wim E.
AU - Van Nostrum, Cornelus F.
PY - 2020/8/3
Y1 - 2020/8/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089575337&partnerID=8YFLogxK
U2 - 10.1021/acs.macromol.0c01031
DO - 10.1021/acs.macromol.0c01031
M3 - Article
C2 - 32884159
AN - SCOPUS:85089575337
SN - 0024-9297
VL - 53
SP - 7009
EP - 7024
JO - Macromolecules
JF - Macromolecules
IS - 16
ER -