Collect. Czech. Chem. Commun. 1995, 60, 1765-1780

Synthesis of Poly(ethylene glycol) Block Copolymers as Potential Water-Soluble Drug Carriers

Michal Pechar, Jiří Strohalm and Karel Ulbrich

Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6, Czech Republic


The synthesis of a model water-soluble drug carrier based on poly(ethylene glycol) (PEG) block copolymers is described. In the copolymers, two blocks of PEG are linked by a biodegradable oligopeptide or amino acid linkage containing the glutamic acid residue. 4-Nitroaniline as a drug model is attached to the γ-carboxyl group of glutamic acid of the polymer carrier via an enzymatically degradable oligopeptide spacer. The oligopeptides used were potential substrates for chymotrypsin. The relationship between the structure of oligopeptides linking two PEG blocks and the rate of chymotrypsin-catalyzed polymer chain degradation as well as the relationship between the structure of the spacer and kinetics of drug model release from the carrier after incubation in chymotrypsin solution is discussed in detail. The results showed that by modifying the structure of oligopeptides in the polymer construct, changes in the rates of both polymer degradation and the drug model release can be achieved in a very broad range.