Transcutaneous delivery of therapeutic agents

Abstract

The present invention provides materials and methods to facilitate the transcutaneous delivery of therapeutic agents. In some embodiments, agonists of tight junctions are used in compositions to facilitate the uptake of therapeutic agents from the skin. In a particular embodiment, the present invention provides immunogenic compositions comprising a tight junction agonist and an antigen. In a particular embodiment, the present invention provides vaccine compositions comprising a tight junction agonist and an antigen.

What is claimed is: 
     
         1 . A transcutaneous dosage composition comprising a therapeutic agent and a transcutaneous absorption enhancing amount of a tight junction agonist, wherein the tight junction agonist is a peptide comprising an amino acid sequence selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (a) 
                 
                     
                   (SEQ ID NO: 1) 
                 
                     
                   Phe Cys Ile Gly Arg Leu; 
                 
                     
                     
                 
                     
                   (b) 
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   Xaa1 Cys Ile Gly Arg Leu; 
                 
                     
                     
                 
                     
                   (c) 
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   Phe Xaa2 Ile Gly Arg Leu; 
                 
                     
                     
                 
                     
                   (d) 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   Phe Cys Xaa3 Gly Arg Leu; 
                 
                     
                     
                 
                     
                   (e) 
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   Phe Cys Ile Xaa4 Arg Leu; 
                 
                     
                     
                 
                     
                   (f) 
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   Phe Cys Ile Gly Xaa5 Leu; 
                 
                     
                     
                 
                     
                   (g) 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   Phe Cys Ile Gly Arg Xaa6; 
                 
                     
                     
                 
                     
                   (h) 
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   Xaa1 Xaa2 Ile Gly Arg Leu; 
                 
                     
                     
                 
                     
                   (i) 
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   Xaa1 Cys Xaa3 Gly Arg Leu; 
                 
                     
                     
                 
                     
                   (j) 
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   Xaa1 Cys Ile Xaa4 Arg Leu; 
                 
                     
                     
                 
                     
                   (k) 
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   Xaa1 Cys Ile Gly Xaa5 Leu; 
                 
                     
                     
                 
                     
                   (l) 
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   Xaa1 Cys Ile Gly Arg Xaa6; 
                 
                     
                     
                 
                     
                   (m) 
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   Phe Xaa2 Xaa3 Gly Arg Leu; 
                 
                     
                     
                 
                     
                   (n) 
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   Phe Xaa2 Ile Xaa4 Arg Leu; 
                 
                     
                     
                 
                     
                   (o) 
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   Phe Xaa2 Ile Gly Xaa5 Leu; 
                 
                     
                     
                 
                     
                   (p) 
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   Phe Xaa2 Ile Gly Arg Xaa6; 
                 
                     
                     
                 
                     
                   (q) 
                 
                     
                   (SEQ ID NO: 17) 
                 
                     
                   Phe Cys Xaa3 Xaa4 Arg Leu; 
                 
                     
                     
                 
                     
                   (r) 
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   Phe Cys Xaa3 Gly Xaa5 Leu; 
                 
                     
                     
                 
                     
                   (s) 
                 
                     
                   (SEQ ID NO: 19) 
                 
                     
                   Phe Cys Xaa3 Gly Arg Xaa6; 
                 
                     
                     
                 
                     
                   (t) 
                 
                     
                   (SEQ ID NO: 20) 
                 
                     
                   Phe Cys Ile Xaa4 Xaa5 Leu; 
                 
                     
                     
                 
                     
                   (u) 
                 
                     
                   (SEQ ID NO: 21) 
                 
                     
                   Phe Cys Ile Xaa4 Arg Xaa6; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (v) 
                 
                     
                   (SEQ ID NO: 22) 
                 
                     
                   Phe Cys Ile Gly Xaa5 Xaa6, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       wherein Xaa1 is selected from the group consisting of Ala, Val, Leu, Ile, Pro, Trp, Tyr, and Met; Xaa2 is selected from the group consisting of Gly, Ser, Thr, Tyr, Asn, and Gln; Xaa3 is selected from the group consisting of Ala, Val, Leu, Ile, Pro, Trp, and Met; Xaa4 is selected from the group consisting of Gly, Ser, Thr, Tyr, Asn, Ala, and Gln: Xaa5 is selected from the group consisting of Lys and His; Xaa6 is selected from the group consisting of Ala, Val, Leu, Ile, Pro, Trp, and Met. 
     
     
         2 . The dosage composition of  claim 1 , wherein the peptide comprises from about 6 to about 10 amino acid residues. 
     
     
         3 . The dosage composition of  claim 1 , wherein the therapeutic agent is selected from the group consisting of antibiotics, anti-inflammatories, analgesics, insulin, vaccines, small molecules, peptides, proteins, lipids, carbohydrates, and combinations thereof. 
     
     
         4 . The dosage composition of  claim 1 , wherein the composition is in a form selected form the group consisting of an aqueous solution and a saline solution. 
     
     
         5 . The dosage composition of  claim 1 , wherein the composition further comprises one or more pharmaceutically acceptable excipients. 
     
     
         6 . The dosage composition of  claim 1 , wherein the therapeutic agent is an antigen. 
     
     
         7 . The dosage composition of  claim 6 , wherein the antigen is selected from the group consisting of measles virus antigens, mumps virus antigens, rubella virus antigens,  Corynebacterium diphtherias  antigens,  Bordetella pertussis  antigens,  Clostridium tetani  antigens,  Bacillus anthracis  antigens,  Haemophilus influenzae  antigens, smallpox virus antigens, and influenza virus antigens. 
     
     
         8 . The dosage composition of  claim 6  further comprising an adjuvant. 
     
     
         9 . A method of treating an animal, comprising: administering to the animal's skin the dosage composition of  claim 1 . 
     
     
         10 . The method of  claim 8 , wherein the animal is human. 
     
     
         11 . A method of treating diabetes in an animal in need thereof, comprising: administering to the animal's skin the dosage composition of  claim 1 , wherein said therapeutic agent is insulin and/or a derivative thereof. 
     
     
         12 . The method of  claim 11 , wherein the animal is human. 
     
     
         13 . A method of inducing an immune response in an animal in need thereof, comprising: administering to the animal's skin the dosage composition of  claim 6 . 
     
     
         14 . The method of  claim 13 , wherein the animal is human. 
     
     
         15 . A method of inducing a protective immune response in an animal in need thereof, comprising: administering to the animal's skin the dosage composition of  claim 6 . 
     
     
         16 . The method of  claim 15 , wherein the animal is human.