具有pH-响应性的聚天冬氨酸类载药胶束的制备和释放能力研究

通过大分子引发剂ω-氨基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和水合肼侧基改性,制备了一系列聚乙二醇-聚氨基酸类三嵌段共聚物.其中聚氨基酸链段包括具有酰肼基的聚天冬氨酸衍生物(PAHy),以及疏水性的聚丙氨酸链段.引入具有pH响应性的腙键键合阿霉素,利用键合阿霉素与游离阿霉素之间的π-π叠合作用,在聚合物自组装形成胶束过程中通过化学键合+物理包埋的方式充分负载药物.该胶束以聚丙氨酸链段为核心,以PEG链段为冠层,以PAHy链段为包裹药物的壳层.载药胶束的粒径在170 nm左右.研究不同pH值条件下载药胶束的药物释放能力,随环境pH值的降低药物的释放速率显著增加.

ANTI-TUMOR DRUG DELIVERY OF A pH-SENSITIVE POLY( ASPARTIC ACID)-CONTAINING BLOCK COPOLYMER

A novel biodegradable ABC type triblock copolymer was synthesized by N-carboxyl anhydride ring-opening polymerization.Triblock copolymer mPEG-poly(asparthyl hydrazide)-PLAla(mPEG-PAHy-PLAla) was synthesized by hydrazine aminolysis.DOX was conjugated to the polymer through a pH-sensitive hydrazone bond.High drug-loaded polymeric micelles were obtained via the π-π interaction between conjugated and free DOX molecules.FTIR,dynamic light scattering,UV and TEM were used in the characterization and measurements.It was found that this polymer/drug complex could form nano-scaled core-shell-corona trilayer particles in aqueous solution.PLAla,PAHy(DOX) and PEG blocks served as the hydrophobic core,pH-sensitive shell and hydrophilic corona,respectively.The drug release experiments displayed a pH-dependent behavior that DOX release rate increased significantly as the environmental pH value dropped from physiologically 7.4 to acidic values resulted from the cleavage of hydrazone bonds and the increasing of hydrophilicity of PAHy segements at lower pH values.This new platform represents a promising candidate in the formulation of targeted drug delivery systems to the low pH tumor tissues.