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

Self-Assembly of Dual-Sensitive mPEG-PDPA-P(AAm-co-AN)for Drug Delivery

设计合成了一种新型两亲性三嵌段ABC聚合物聚乙二醇单甲醚-聚甲基丙烯酸二异丙胺基乙酯-聚(丙烯酰胺-co-丙烯腈)(mPEG-PDPA-P(AAm-co-AN))。该聚合物具有pH敏感嵌段PDPA和温度敏感嵌段P(AAm-co-AN),临界溶解温度(UCST)较高,且可以通过改变单体比例来调节UCST。在室温、中性环境下,该聚合物通过自组装形成刺激响应型胶束,可用于抗肿瘤药物的控释研究。温度升高诱导聚合物胶束向不对称囊泡结构转变,pH降低促使聚合物形成更加松散的胶束。在体外释药探究中,聚合物胶束对亲水药物阿霉素(DOX)和疏水药物槲皮素都具有良好的载药效果,在37℃、pH=7.4的条件下泄漏量低,随着温度升高和pH降低,胶束释放药物的速率和释放量明显增加。

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.