STARCH MICROSPHERES INDUCE PULSATILE DELIVERY OF DRUGS AND PEPTIDES ACROSS THE EPITHELIAL BARRIER BY REVERSIBLE SEPARATION OF THE TIGHT JUNCTIONS

Non-parenteral administration of peptide drugs is prevented by the lim ited permeability of the epithelia lining the mucosal tissues. As a ne w approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. Th e microspheres induced a pulsed delivery of insulin across the epithel ium that lasted for 1-2 h. The pulsed delivery correlated with a rever sible appearance of focal dilatations in the tight junctions between t he epithelial cells, indicating that dsm enhance the delivery of insul in by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm.