Compositions and methods for enhancing drug delivery across and into epithelial tissues

Abstract

This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidine or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

What is claimed is: 
     
         1 . A method of targeting a compound to a gastrointestinal epithelium of an animal, the method comprising administering to the gastrointestinal epithelium a conjugate comprising the compound and a delivery-enhancing transporter, wherein:
 i. the compound is attached to the delivery-enhancing transporter through a linker; and   ii. the delivery-enhancing transporter comprises fewer than 50 subunits and comprises at least 5 guanidine or amidino moieties, thereby increasing delivery of the conjugate into the gastrointestinal epithelium compared to delivery of the compound in the absence of the delivery-enhancing transporter.   
     
     
         2 . A. method for enhancing delivery of a compound into and across one or more layers of an animal ocular epithelial tissue, the method comprising:
 administering to the ocular epithelial tissue a conjugate comprising the compound and a delivery-enhancing transporter,   wherein:   i. the compound is attached to the delivery-enhancing transporter through a linker, and   ii. the delivery-enhancing transporter comprises fewer than 50 subunits and comprises at least 5 guanidino or amidino moieties, thereby increasing delivery of the conjugate into the gastrointestinal epithelium compared to delivery of the compound in the absence of the delivery-enhancing transporter.