| 摘要 |
Compositions and methods are provided that include a biologically active age nt and a permeabilizing agent effective to enhance mucosal delivery of the biologically active agent in a mammalian subject. The permeabilizing agent reversibly enhances mucosal epithelial paracellular transport, typically by modulating epithelial junctional structure and/or physiology at a mucosal epithelial surface in the subject. This effect typically involves inhibition by the permeabilizing agent of homotypic or heterotypic binding between epithelial membrane adhesive proteins of neighboring epithelial cells. Targe t proteins for this blockade of homotypic or heterotypic binding can be select ed from various related junctional adhesion molecules (JAMs), occludins, or claudins. The permeabilizing agent is typically a peptide or peptide analog or mimetic, often selected or derived from an extracellular domain of a mammali an JAM, occludin or claudin protein. |
