Synthesis Of Thermo-Sensitive Amphiphilic Graft Copolymers And Their Self-Assembly

The hydroxyl-terminated Poly(N-isopropylacrylamide -co-N,N-dimethylacrylamide -co- 2-hydroxyethyl methacrylate)[Poly(NIPAAm-co-DMAAm-co-HEMA)] were synthesized by free radical solution copolymerization using thioglycol as chain transfer agent. Amphipathic graft copolymers, poly(N-isopropylacrylamide -co-N,N-dimethylacrylamide -co- 2-hydroxyethyl methacrylate) -graft-Polycaprolactone [Poly(NIPAAm-co-DMAAm-co-HEMA)-g-PCL], were prepared via bulk ring-opening polymerization of CL by using the pendant and terminated hydroxyl groups of main chain as initiators. The obtained polymers were characterized by ~1H-NMR and GPC analysis. And the thermal transitions of these copolymers were characterized by measuring the transmittance of aqueous polymeric solutions, and the temperature of the point of 50% transmittance was identified as low critical solution temperature (LCST). Then a series of micelle solutions were prepared in selective solvents by means of self-assembly. The critical micellar concentration (CMC) and micelle diameter were studied by fluorescent probe technique with pyrene as a probe molecule and dynamic light scattering measurement respectively. In result, With incorporation of hydrophilic DMAAm, Poly(NIPAAm-co-DMAAm-co-HEMA) copolymers showed markedly increase in LCST. On the contrary, HEMA contributed different LCST behaviors from DMAAm. With the incorporation of HEMA which is also a hydrophilic monomer the LCST shift to a lowe temperature, Above these, a series of Poly(NIPAAm-co-DMAAm-co-HEMA) copolymers with LCST of～40℃, which contained both hydroxyl at chain end and different amount of pendent hydroxyl groups, were obtained and adjusting the molar ratio of NIPAAm, DMAAm and HEMA. The LCST of the grafted amphiphilic copolymers shifted to lower values with the introduction of hydrophobic PCL chains onto hydrophilic backbone. And their thermal sensitivity decreased with the amount and length of side PCL chains being increased. The CMC of the copolymers decreased with the increase of the side PCL chain length, the micelle sizes were largely influenced by the hydrophobic chaincontent too.Ideally, thermal sensitive micelles prepared from these amphiphilic copolymers would be good candidates for target or "smart" drug controlled delivery to treat diseases, such as solid tumor in combination with local hyperthermia therapy.