Wennink - Introducing small cationic groups into 4-armed PLLAePEG copolymers leads to preferred micellization over thermo-reversible gelation

J.W.H. Wennink, F. Signori, M. Karperien, S. Bronco, J. Feijen, P.J. Dijkstra

Polymer - 2013

Abstract

Starting from bis-MPA, PEGePLLA triblock copolymers (bis-MPA-(PLLAePEG)2), comprising a central Nhydroxysuccinimide
active ester, were synthesized. Reacting the corresponding active ester with a,udiamines
afforded four-armed (PEGePLLA)2eRe(PLLAePEG)2 copolymers with central a,u-diamide
groups (R). Applying the a,u-diamines, hexamethylene-diamine, spermine or norspermidine none, one
or two secondary amine groups, respectively, were introduced into the linking moiety R. Whereas a
copolymer containing no secondary amine groups showed fully thermo-reversible gelation behavior,
copolymers comprising a central moiety containing one or two secondary amine groups retained the ‘sol’
state after a few heating and cooling cycles. Dynamic light scattering revealed that the copolymer
containing no secondary amine groups showed a thermo-reversible shift in micellar size and small
aggregates (57 and 877 nm at 25 C and 40 and 152 nm at 50 C). Conversely, copolymers comprising a
central moiety containing secondary amine groups show a temperature independent distribution mainly
consisting of micelles. It is proposed that the protonated amine groups preferably are located at the
corona of the micelles and micellar aggregates and/or shielded by the PEG blocks, hindering the formation
of hydrogels by PEG entanglements upon a change in temperature.