Compositions for prevention of adhesions and other barrier applications
A method has been developed of preventing or limiting formation of adhesions by administering to a site in need thereof, in the absence of or after bleeding or leakage of fluid has been substantially stopped, a self-assembling material which forms a barrier to formation of adhesions. In certain embodiments, the self assembling materials are peptidomimetics, nucleotidomimetics, di- and triblock copolymers, N-alkylacrylamides, or dendimers. These materials are also useful in a method for regeneration or repair of tissue or cells forming tissue.
1. A method of preventing or limiting formation of scar tissue at a wound or surgery site or a site of inflammation comprising
topically administering to diseased or damaged skin or epithelial tissue a formulation comprising self-assembling peptides which form a barrier to contamination and loss of fluid from the diseased or damaged skin or epithelial tissue,
wherein the formulation does not include cells, and
wherein the barrier is effective to reduce or prevent the formation of scar tissue at the site of administration relative to an untreated control.
2. The method of claim 1 , wherein the self-assembling peptides comprise a sequence of amino acid residues conforming to one or more of Formulas I-IV:
((Xaa neu -Xaa + )x(Xaa neu -Xaa − )y)n (I)
((Xaa neu -Xaa − )x(Xaa neu -Xaa + )y)n (II)
((Xaa + -Xaa neu )x(Xaa − -Xaa neu )y)n (III)
((Xaa − -Xaa neu )x(Xaa + -Xaa neu )y)n (IV)
wherein: Xaa neu is an amino acid residue having a neutral charge; Xaa + is an amino acid residue having a positive charge; Xaa 31 is an amino acid residue having a negative charge; x and y are integers having a value of 1, 2 or 4, independently; and n is an integer having a value of 1-5.
3. The method of claim 2 , wherein the self-assembling peptides comprise a sequence of amino acid residues conforming to Formula III or Formula IV.
4. The method of claim 3 , wherein Xaa neu is alanine, or leucine, or isoleucine; Xaa + is arginine or lysine; and Xaa 31 is aspartic acid or glutamic acid.
5. The method of claim 2 , wherein the self-assembling peptides comprise the amino acid sequence RADARADARADARADA (SEQ ID NO: 1).
6. The method of claim 1 , wherein the self-assembling peptides are administered to damaged skin or mucosal tissue that is not bleeding.
7. The method of claim 1 , further comprising providing one or more therapeutic, prophylactic, or diagnostic agents.
8. The method of claim 1 , wherein the formulation further comprises a pharmaceutically acceptable material for administration to diseased or damaged skin or mucosa.
9. The method of claim 8 wherein the formulation is in a form selected from the group consisting of a dry powder, wafer, disk, tablet, capsule, liquid, gel, cream, foam, ointment, emulsion, suspension, solution, a coating on a medical device, microparticles, polymeric matrices, hydrogels, textile, suture, and a sponge.
10. The method of claim 9 , wherein the self-assembling peptides are applied in the form of a solution.
11. The method of claim 10 , further comprising the step of forming the solution by dissolving a powder of the self-assembling peptides with water or oil.
12. The method of claim 11 , wherein the concentration of self-assembling peptides in the solution is between 2% wt/vol and 3% wt/vol, inclusive.
13. The method of claim 1 , wherein the self-assembling peptides are administered to the site of a surgical procedure at a time point selected from group consisting of before the initiation of the surgical procedure; during the surgical procedure; after commencement of the surgical procedure; and combinations thereof.
14. The method of claim 1 , wherein the self-assembling peptides are administered to the surface of skin at the site of a burn.
15. The method of claim 1 , wherein the self-assembling peptides are administered to the surface of skin at the site of a laceration.
16. The method of claim 1 , wherein the self-assembling peptides are administered to the surface of skin at the site of an ulcer.
17. The method of claim 1 , wherein the formulation of self-assembling peptides comprises a concentration of Li+, Na+, K+, and Cs+ ions less than 5 mM.
18. The method of claim 1 , wherein the self-assembling peptides are in a solution having a concentration of self-assembling peptides between 1.0% and 10.0%, inclusive.
19. The method of claim 1 , wherein the self-assembling peptides are administered to damaged skin or mucosal tissue that is bleeding, and
wherein the self-assembled barrier structure is maintained in contact with the tissue following the cessation of bleeding.