Polymeric prodrugs.

Abstract

Polymeric prodrugs can be defined as latent pharmaceutical agents which must undergo chemical or enzymatic transformation to the active or parent drug in the organism after administration. Polymeric prodrugs may also be considered special types of drug delivery systems where the drug release is realized by cleavage of a chemical bond. The concept of polymeric prodrugs finds application in the design of novel agents when pharmacokinetical modification of a parent drug is necessary, or when the aim is to achieve selective action at a target site, utilizing enzymatic activation specific for that site. The types of polymeric prodrugs synthetized in the last decade are reviewed regarding the chemical structure of the carrier backbone and the drug linkages applied. Relationship between the chemical structure, physicochemical characteristics of polymeric prodrugs, and their physiological behavior is discussed, with special regard to the bioavailability, body distribution, and rate of elimination of the carrier from the living organism. In vitro and in vivo experimental data concerning drug activation processes, as well as potential clinical applications of polymeric prodrugs, are surveyed.