Current strategies used to enhance the paracellular transport of therapeutic polypeptides across the intestinal epithelium

The intent of this paper is to update the reader on various strategies which have been utilized to increase the paracellular permeability of protein and polypeptide drugs across the intestinal epithelium. Structural features of protein and polypeptide drugs, together with the natural anatomical and physiological features of the gastrointestinal (GI) tract, have made oral delivery of this class of compounds extremely challenging. Interest in the paracellular route for the transport of therapeutic proteins and polypeptides following oral administration has recently intensified and continues to be explored. The assumption that molecules with a large molecular weight are not able to diffuse through the tight junctions of the intestinal membrane has been challenged by current research, along with an increased understanding of tight junction physiology. (c) 2005 Elsevier B.V. All rights reserved.