Crosslinked poly-γ-glutamic acid based nanosystem for drug delivery

This study describes a method for the preparation of targeted drug delivery nanosystem from a water-soluble, biodegradable polymer by crosslinking. The nanosystem consists of poly-gamma-glutamic acid as carrier, doxorubicin as active ingredient, and folic acid as targeting agent. Crosslinks were made between the monomer units of poly-gamma-glutamic acid using a short spacer, which coupled and compressed the polymer chains and formed nanoparticles. Folic acid was conjugated through poly(ethylene-glycol) directly to the polymer before crosslinking, and also to the surface of the prepared nanoparticles, thus an enhanced targeting effect was provided. The encapsulation of the active ingredient was done by trapping it between the crosslinks. Using appropriate reaction conditions, the thus formed nanosystem had an average size of 140-200 nm, slightly negative surface charge, and retained its stability for several months at 4 degrees C in aqueous medium. Pharmacokinetic studies demonstrated that greater amount of doxorubicin can reach the tumor tissue in case of nanoparticles compared to the free drug molecules. In vivo antitumor study revealed better inhibitory effect on tumor growth in the crosslinked nanoparticles-treated animals than those treated by free drug, and the overall survival was also better.