双重敏感mPEG-PDPA-P(AAm-co-AN) 聚合物 自组装体的药物递送.

Poly(ethylene glycol) monomethyl ether-poly(2-diisopropylaminoethyl methacry-late)-poly(acrylamide-coacrylonitrile) (mPEG-PDPA-P(AAm-co-AN)), a novel amphiphilic triblock ABC polymer, was designed and synthesized. This polymer was prepared by atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer polymerization (RAFT). When pH changes, PDPA undergoes a hydrophilic-hydrophobic transition. Therefore, the polymer has pH-responsivity with a pH-sensitive point at pH 6.53. The P(AAm-co-AN) fragment forms hydrogen bonds at low temperature. At high temperature, hydrogen bonds are formed between the polymer chains and water molecules so that the polymer mPEG-PDPA-P(AAm-co-AN) has a high critical solution temperature (UCST). By varying the monomer ratios of acrylamide (AAm) to acrylonitrile (AN) and the concentration of the solution, polymers with different UCSTs can be obtained. In a neutral environment at room temperature, the polymer solution forms micelles by self-assembly with mPEG as the shell and PDPA and P(AAm-co-AN) as the core. The particle size, potential and morphology of the micelles in various external environments were studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). An increase in temperature induces a transition from micelles to asymmetric vesicles. The lower pH encourages the polymer to form looser micelles. Simultaneously changing the pH and temperature, the hydrophilicity of each block of the polymer increases, the micelles dissolve sufficiently, and the particle size increases. In an in vitro drug release investigation, polymeric micelles show good drug delivery for both the hydrophilic drug doxorubicin (DOX) and the hydrophobic drug quercetin. The micelles show low leakage at 37 ℃ and pH 7.4. The release rate of drug from the micelles increases significantly with the increasing of temperature and the decreasing of pH. It is demonstrated that the polymeric micelles have good environmental stimulus sensing ability and controlled drug release. [ABSTRACT FROM AUTHOR]