BIODEGRADABLE DRUG CARRIERS BASED ON POLY(ETHYLENE GLYCOL) BLOCK-COPOLYMERS

The synthesis of a model water-soluble drug carrier system based on po ly(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 gamma-carboxyl group o f glutamic acid of the polymer carrier via an enzymatically degradable oligopeptide spacer. All oligopeptides were prepared as potential sub strates for cathepsin B, a representative of lysosomal enzymes. The re lationship between the structure of oligopeptides forming the linkage between two PEG molecules and the rate of cathepsin B-catalyzed polyme r chain degradation is evaluated. The relationship between the structu re of the spacer and kinetics of drug model release from the carrier a fter incubation in cathepsin B solution is also discussed in detail. T he results show that, by altering the structure of oligopeptides in th e polymer construct, marked changes in the rate of both polymer degrad ation and the drug model release can be achieved.