Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 420, Issue 2, Pages 333-340Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2011.08.038
Keywords
Thermo-responsive; Shell cross-linked (SCL) micelle; RAFT; Controlled drug release
Categories
Funding
- Ministry of Science and Technology of China [2011CB606202, 2009CB930300]
- Trans (New)-Century Training Programme Foundation for the Talents from the Ministry of Education of China
- Natural Science Foundation of Hubei Province, China [2009CDA024]
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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 degrees C and 40.8 degrees 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 degrees 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. (c) 2011 Elsevier B.V. All rights reserved.
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