A mechanistic analysis of carrier-mediated oral delivery of protein therapeutics

This article summarizes the results of a theoretical analysis of protein ab sorption into the systemic circulation from the small intestine, with and w ithout molecular 'carriers' designed to enhance absorption. The predictions are compared with experimental systemic protein concentrations following i ntraduodenal delivery of insulin, interferon alpha-2b, and human growth hor mone. The results show that, from the standpoint of improving oral absorpti on, the primary consequence of carrier molecules is to increase epithelial membrane permeability, thereby leading to higher bioavailability. Several p ossible mechanisms of this permeability enhancement are discussed. (C) 2000 Elsevier Science B.V. All rights reserved.