Biodegradable drug carriers based on poly(ethylene glycol) block copolymers

Abstract

The synthesis of a model water-soluble drug carrier system based on poly(ethylene glycol) (PEG) block copolymers is described. In the system, two blocks of PEG are connected via a biodegradable oligopeptide or amino acid linkage incorporating at least one glutamic acid residue. A drug model (4-nitroaniline) is attached to the γ-carboxyl group of glutamic acid of the polymer carrier via an enzymatically degradable oligopeptide spacer. All oligopeptides were prepared as potential substrates for cathepsin B, a representative of lysosomal enzymes. The relationship between the structure of oligopeptides forming the linkage between two PEG molecules and the rate of cathepsin B-catalyzed polymer chain degradation is evaluated. The relationship between the structure of the spacer and kinetics of drug model release from the carrier after incubation in cathepsin B solution is also discussed in detail. The results show that, by altering the structure of oligopeptides in the polymer construct, marked changes in the rate of both polymer degradation and the drug model release can be achieved.