Thermo-responsive shell cross-linked PMMA-b-P(NIPAAm-co-NAS) micelles for drug delivery

Thermo-responsive amphiphilic poly(methyl methacrylate)-b-poly(N-isopropylacrylamide-co-N-acryloxysuccinimide) (PMMA-b-P(NIPAAm-co-NAS)) block copolymer was synthesized by successive RAFT polymerizations. The uncross-linked micelles were facilely prepared by directly dissolving the block copolymer in an aqueous medium, and the shell cross-linked (SCL) micelles were further fabricated by the addition of ethylenediamine as a di-functional cross-linker into the micellar solution. Optical absorption measurements showed that the LCST of uncross-linked and cross-linked micelles was 31.0 °C and 40.8 °C, respectively. Transmission electron microscopy (TEM) showed that both uncross-linked and cross-linked micelles exhibited well-defined spherical shape in aqueous phase at room temperature, while the SCL micelles were able to retain the spherical shape with relatively smaller dimension even at 40 °C due to the cross-linked structure. In vitro drug release study demonstrated a slower and more sustained drug release behavior from the SCL micelles at high temperature as compared with the release profile of uncross-linked micelles, indicating the great potential of SCL micelles developed herein as novel smart carriers for controlled drug release.

Graphical abstractThermo-responsive shell cross-linked (SCL) micelles were fabricated based on PMMA-b-P(NIPAAm-co-NAS) copolymer using ethylenediamine as a di-functional cross-linker. Due to the cross-linked structure, the resultant SCL micelles were able to maintain well-defined spherical shape in organic solvent as well as at high temperature. Most importantly, the SCL micelles exhibited more sustained drug release behavior than uncross-linked micelles at high temperature.Figure optionsDownload full-size imageDownload as PowerPoint slide