Influence of indomethacin-loading on the micellization and drug release of thermosensitive dextran-graft-poly(N-isopropylacrylamide)

The influence of loading indomethacin (IMC) on the thermosensitive aggregation of a double hydrophilic graft copolymer dextran-graft-poly(N-isopropylacrylamide) (DgP) was studied. Before IMC-loading, DgP forms loose aggregates of unimers in aqueous solution below the lower critical solution temperature (LCST), while compact nanoparticles appear above the LCST because of the phase transition of the poly(N-isopropylacrylamide) (PNIPAAm) side chains (Topp, 1997 [31]; Motokawa, 2005 [32]; Zhao, 2006 [25]). After the loading of IMC, however, uniform nanoparticles were formed even below the LCST. The hydrogen bonding between IMC and the PNIPAAm side chains is proposed as the driving force for the aggregation. The IMC release rate was accelerated at a higher temperature because of the dissociation of the hydrogen bonds.