ABSTRACT
BACKGROUND: Polymer micelles is a new type of drug carriers developed in recent years,with a wide range of carrying drugs,structural stability,excellent tissue permeability,long residence of drugs in vivo,and effective reaching the target.The performances of intelligent targeting and decreasing the initial burst release have become the focus of recent researches.OBJECTIVE: To obtain an intelligent targeting drug carrier of low critical solution temperature(LCST)at 40℃,to change drug release behavior through the changes of temperature,and to further improve the stability and drug release behavior of the micelles by core-crosslinking.METHODS: By radical polymerization of N-isopropylacrylamide(NIPAAm)and N,N-dimethylacrylamide(DMAAm),hydroxyl terminated poly(N-isopropylacrylamide-co-N,N-dimethyl acrylamide)[P(NIPAAm-co-DMAAm)]was synthesized.Molecular weight and LCST of P(NIPAAm-co-DMAAm)were regulated by adjusting the mercaptoethanol and monomer ratio,as well as the ratio of NIPAAm and DMAAm,Amphiphilic block copolymer P(NIPAAm-CO-DMAAm)-b-PCL was prepared via bulk ring-opening polymerization of ε-caprolactone by using the end hydroxyl group of P(NIPAAm-co-DMAAm)as initiator and stannous octoate as catalyst.The block copolymer reacted with acryloyl chloride to obtain amphiphilic block copolymers with unsaturated double bonds at the terminal.Drug loaded nano-micelles with different nuclear cross-linked degrees were prepared by dialysis method,and its release behavior was investigated.RESULTS AND CONCLUSION: Amphiphilic block copolymers,with the LCST of 42℃,were obtained with hydroxyl or acryloyl endgroup.By blending them at different ratios,thermo-sensitive drug-loaded nano-micelles with different core-cresslinking degrees were prepared.The drug release rate was faster at 43℃ than at 37℃.With the core-crosslinking degrees increasing,the release of paclitaxel gradually slowed.The results suggest that the drug release rate from micelles prepared from thermo-sensitive P(NIPAAm-co-DMAAm)-b-PCL can be regulated by the degree of cross-linking.