Compositions and methods for affecting movement of contaminants, bodily fluids or other entities, and/or affecting other physiological conditions
Compositions which self-assemble under physiological conditions are formulated for application to wounds. The formulations include a pharmaceutically acceptable carrier or are provided as part of a medical device or coating. The formulations may also include other therapeutic, prophylactic or diagnostic agents. The formulation can be administered as appropriate for treatment of one or more disorders or conditions. For example, the formulation may be applied to repair an injury or during surgery of the lung, eye or dura, or following an epidural or spinal tap, to stop leakage of blood, interstitial fluid, or cerebrospinal fluid.
1. An in vivo barrier structure, comprising:
a composition comprising self-assembled peptidomimetics comprising alternating hydrophobic and hydrophilic residues and alternating positively-charged and negatively-charged residues,
wherein the peptidomimetics are selected from the group consisting of α-peptides, β-peptides, γ-peptides, and δ-peptides,
wherein the α-peptide peptidomimetics are selected from the group consisting of N,N′-linked oligoureas, oligopyrrolinones, oxazolidin-2-ones, azatides and azapeptides, and
wherein the barrier structure is formed following contact of the peptidomimetics with a bodily fluid and/or contaminant of a tissue.
2. The structure as in claim 1 , wherein the bodily fluid is blood, plasma, interstitial fluid, cerebral spinal fluid, tissue fluids, fluid produced by a parenchymal tissue, serous exudate, pus, gastric juice, urine, or bile.
3. The structure as in claim 1 , wherein the bodily fluid is blood.
4. The structure as in claim 1 , wherein the contaminant comprises bacteria, cells, infection, pus, serous exudate, bile, pancreatic fluid, or a substance contained within the stomach, intestine, or urinary tract, or an airborne contaminant.
5. The structure as in claim 1 , wherein the structure further comprises a therapeutic agent, a prophylactic agent, a diagnostic agent, a pharmaceutically acceptable diluent, filler, or a stabilizing agent.
6. The structure as in claim 5 , wherein the structure further comprises anti-inflammatories, vasoconstrictors, anti-infectives, anesthetics, growth factors, cells, organic compounds, coloring agents, vitamins, or metals.
7. The structure as in claim 1 , wherein the barrier structure changes in phase relative to the composition prior to contact with the bodily fluid and/or contaminant.
8. The structure as in claim 1 , wherein the peptidomimetics self-assemble into a plurality of nanofibers.
9. The structure as in claim 8 , wherein each nanofiber of the plurality of nanofibers has a diameter of approximately 10-20 nm.
10. The structure as in claim 1 , wherein the bodily fluid and/or contaminant of the animal comprises at least one ionic species.
11. The structure as in claim 10 , wherein the ionic species is a monovalent cation, a divalent cation, or a trivalent cation.
12. The structure as in claim 11 , wherein the ionic species is Li + , Na + , K + , or Cs + .
13. The structure as in claim 1 , wherein the hydrophilic residues alternate with one positively charged and one negatively charged residue.
14. The structure as in claim 1 , wherein the hydrophilic residues alternate with two positively charged and two negatively charged residues.
15. The structure as in claim 1 , wherein the hydrophilic residues alternate with three positively charged and three negatively charged residues.
16. The structure as in claim 1 , wherein the hydrophilic residues alternate with four positively charged and four negatively charged residues.
17. A composition, comprising:
self-assembling peptidomimetics, wherein the peptidomimetics comprise alternating hydrophobic and hydrophilic residues, and alternating positively-charged and negatively-charged residues,
wherein the peptidomimetics are selected from the group consisting of α-peptides, β-peptides, γ-peptides, and δ-peptides,
wherein the α-peptide peptidomimetics are selected from the group consisting of N,N′-linked oligoureas, oligopyrrolinones, oxazolidin-2-ones, azatides and azapeptides, and
wherein the composition forms a structure following contact of the peptidomimetics with a bodily fluid of a tissue and
wherein the structure inhibits movement of a bodily fluid and/or contaminant of a tissue.
18. The composition as in claim 17 , wherein the peptidomimetics are in solid form.
19. The composition as in claim 17 , wherein the peptidomimetics are contained in solution.
20. The composition as in claim 18 , wherein the solid is a spray; a powder or a lyophilized powder; or a plurality of pellets, granules, or particles.
21. The composition as in claim 17 , wherein the composition further comprises a nasal plug, a bandage, a suture, a tape, an adhesive, a surgical drape, a foam, or a matrix.
22. The composition as in claim 17 , wherein the composition is a gel or a foam.
23. A kit comprising the composition as in claim 17 , and instructions for use in inhibiting movement of a bodily fluid and/or contaminant in or out of a wound or site of injury or surgery of a tissue.
24. The kit as in claim 23 , wherein the kit further comprises a syringe or vessel comprising one or more compartments, wherein a first compartment comprises the composition and a second compartment comprises a solution which, when combined with the composition, dissolves or hydrates the composition to form a material that inhibits movement of a bodily fluid and/or contaminant.
25. The composition as in claim 17 , wherein the structure is formed upon interaction of the peptidomimetics with at least one ionic species present in or on the tissue.
26. The composition as in claim 19 , wherein the solution is water.