Star-Block Copolymer-Based Drug Carriers And Their PH-responsive Releasing Properties

The research mainly aimed to synthesize a new type of star-block copolymers as a potential drug carrier, and to investigate its drug-loading capacity as well as the pH-responsive releasing property. The synthesized core-shell star-block copolymer consisted of a low-molecular-weight hyperbranched polyethyleneimine (PEI) core, a biodegradable poly(glutamic acid) (PLGA) inner shell, and a water-soluble and biocompatible poly(ethylene glycol) (PEG) outer shell. High purity amino acid N-carboxylanhydrides (NCA) of y-benzyl L-glutamate (BLG) was synthesized by phosgenation in ethyl acetate, and its subsequent polymerization was initiated by the amine groups in the periphery of polyethyleneimine (PEI) to prepare star poly(benzyl glutamate) (PEI-PBLG). The side chains of star poly(benzyl glutamate) was then deprotected by HBr in dichloroacetic acid to yield star poly(glutamic acid) (PEI-PLGA) The activated polyethyleneglycol(mPEG) was then attached to the periphery of PEI-PLGA in phosphate buffer to obtain the final star-block copolymer PEI-PLGA-b-mPEG Cationic model compounds can be efficiently encapsulated in the synthesized star-block copolymer via electrostatic interactions under physiologic pH. The model compound crystal violet (CV) or the model drug adriamycin (ADR) was mixed with PEI-PLGA-mPEG, dialyzed against water thoroughly, the loading capacities of model compounds were then detected by UV-Vis spectroscopy. The copolymer-model compound complex was dialyzed against aqueous solution with different pH to determine the releasing curve of the encapsulated model compounds. The releasing rate of loaded model compounds increased remarkably with the decreasing pH. The effect of the PEI core size and the length of PLGA inner shell on the loading capacity and the releasing kinetics were investigated. In conclusion, a novel class of poly(L-glutamic acid)-based star-block copolymers PEI-PLGA-b-mPEG has been developed as a potential drug carriers. This kind of polymer showed efficient encapsulation of cationic compounds and pH-responsive release, and, therefore, could be potentially used for controlled drug delivery.