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 pi-pi 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.