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

This article summarizes the results of a theoretical analysis of protein absorption into the systemic circulation from the small intestine, with and without molecular ‘carriers’ designed to enhance absorption. The predictions are compared with experimental systemic protein concentrations following intraduodenal delivery of insulin, interferon alpha-2b, and human growth hormone. The results show that, from the standpoint of improving oral absorption, the primary consequence of carrier molecules is to increase epithelial membrane permeability, thereby leading to higher bioavailability. Several possible mechanisms of this permeability enhancement are discussed.