Research On Thermo-and PH-Responsive Core-Shell-Corona Micelles From Self-Assembled Triblock Copolymer

Stimuli-responsive copolymers whose behaviors depend strongly on the external chemical and physical stimuli have attracted increasing research attentions for the wide range of applications. In the thesis, we adopted chitosan which is bio-compatibility and high-yield source to prepare responsive copolymer nanomicelle. In our research, copolymers with chitosan as main chain and poly(N-vinylcaprolactam) (PNVCL) as thermo-responsive material and poly(acrylic acid) (PAA) as pH-responsive material were prepared by free-radical polymerization. The structure of (N-CS)-g-P(NVCL-co-AA) was affirmed by FT-IR and 1HNMR; DLS and TEM were used to character the micellization of copolymers, the influence of the micellar morphologies and the ordered aggregation of the miceIles induced by extemal environment; and the release behavior of drug-loaded micelles was researched.The results showed that (N-CS)-g-P(NVCL-co-AA) self-assembled into spherical core-shell micelles with hydrophobic chitosan segments as the core,hydrophilic PAA/PNVCL segments as the mixed shell at 37℃and pH=7.4. Increasing temperatures to 42℃, core-shell micelles converted into narrowly distributed core-shell-corona (CSC) nanomicelles with chitosan as the core,collapsed PNVCL as the shell and soluble PAA as the corona. Moreover,decreasing pH at 37℃, PAA chains collapsed onto the core resulting in CSC micelles with chitosan as the core,PAA as the shell and PNVCL as the corona. Increasing temperatures or decreasing pH values,the micelles converted into core-shell-corona structures with hydrophobic chitosan as the dense core surrounded by collapsed PNVCL blocks or PAA blocks as the shell and soluble PAA chains or PNVCL chains as the corona to protect the micel1es. All the phase behaviors were reversible. The in vitro release results, 5-Fu as model drug, showed the release behavior can divide to sharp release and relaxedly release periods, and the nanomicelles behaved as thermo- and pH-sensitive in the release process.