Prodrugs of peptides and proteins for improved formulation and delivery.

Abstract

This paper aims to review the existing literature on the use of prodrugs to circumvent some of the difficulties associated with the formulation, systemic delivery, and rapid clearance of peptide and protein therapeutic agents. Understanding the basic elements involved in effective delivery and formulation of peptides and proteins is both intellectually challenging and enormously important. The relatively recent evolution of recombinant DNA research and modem synthetic methodologies allow the biochemist and chemist to produce vast quantities of various peptides and proteins possessing pharmacological efficacy. However, the therapeutic potential of these compounds lies in our ability to design and achieve effective and, stable delivery systems. The future challenge in biotechnology may not only be polypeptide cloning and synthesis but effective nonparenteral delivery of intact peptides and proteins to the systemic circulation and their site of action. Based on our current understanding of biochemical and physiological aspects of peptide and protein absorption and metabolism, it is difficult to conceive of efficient means of delivering of these agents through the use of conventional formulation technology, namely, simple tablets and capsules (1-2). The main impediment to the use of peptides and proteins as potential therapeutic drugs is their inadequate and erratic oral absorption (3, 4). Most linear peptides undergo rapid and extensive metabolism by proteolysis in the