Polymer-bound enzyme inhibitors: synthesis, properties, and physiological relevance

For the most part, the pharmacological effect of an enzyme inhibitor results from its interaction with a single target molecule--the target enzyme. In many cases, the inhibitor moiety can interact effectively with the enzyme without necessarily being released from the polymer carrier. In the simplest form, i.e., the inhibition of an extracellular enzyme, this interaction can be understood as being two macromolecules in a solution--a reaction that can be readily modeled in vitro. Thus, enzyme inhibitors are very suitable for preparing polymer-bound drugs for investigative purposes or therapeutical applications. The macromolecular properties of polymers impact on the pharmacokinetic behavior of the compound because of the controlled intercompartmental transport. The physiological significance of the polymer-bound enzyme inhibitors is considered herein regarding the factors controlling the biodistribution of polymers among the physiological compartments. Extracellular proteinases and lysosomal enzymes are the most easily approachable targets. Strategies for preparation of polymer-bound inhibitors are discussed.