US 6,593,292 B1 · 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, 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 guanidino 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.

Claims134

Dependent claims

A method for enhancing delivery of a compound into and across one or more layers of an animal epithelial or endothelial tissue, the method comprising:

contacting the endothelial or epithelial tissue with a conjugate that comprises the compound attached to a delivery-enhancing transporter by a linker,
wherein the delivery-enhancing transporter comprises sufficient guanidino or amidino moieties to increase delivery of the conjugate into and across one or more intact epithelial or endothelial tissue layers compared to delivery of the compound in the absence of the delivery-enhancing transporter;
and
the conjugate has a structure selected from the group consisting of structures 3, 4, 5 and 6, as follows:
wherein:
R1—X comprises the compound;
X is a functional group on the compound to which the linker is attached;
Y is N or CH;
R2 is hydrogen, alkyl, aryl, acyl, or allyl;
R3 comprises the delivery-enhancing transporter;
R4 is unsubstituted O, substituted N or C or substituted or unsubstituted S;
R5 is OH, SH or NHR6;
R6 is hydrogen, alkyl, aryl, acyl or allyl;
k and m are each independently selected from 1 and 2;
n is 1 to 10;
and
Ar is an aryl group having the attached radicals arranged in an ortho or para configuration, which aryl group can be substituted or unsubstituted.

14 more elements

Dependencies are inferred from the claim text.

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

Life of this patent

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

Life of this patent

Abstract

Claims134