Controlled biodegradability of polymers--a key to drug delivery systems.

By combining oligopeptide sequences with synthetic polymeric chains, carriers of drug models can be prepared. The drug model (p-nitroaniline) is cleaved from the carrier in the lysosomal compartment of the cell. By changing the length and structure of the oligopeptide sequence, it is possible to regulate the rate of cleavage of drug model by individual thiol proteinases (cathepsins B, H and L) which are the most important as regards cleavage of the substrates studied. By connecting synthetic polymeric chains via oligopeptide bridges, it is possible to regulate the molecular weight as well as the biodegradability of the carrier molecule. Molecular weight also influences other biological properties, e.g., elimination from the organism, rate of pinocytic uptake and biological activity. Homopolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) is nonimmunogenic in rats. Attachment of oligopeptide side chains gives rise to a macromolecule possessing immunogenic activity. The degree of antibody response depends on the detailed structure of the copolymer.