Self-assembled gels formed with anti-retroviral drugs, prodrugs thereof, and pharmaceutical uses thereof

Abstract

Self-assembled gels and methods of making thereof are described. A selective range of ratios between an organic solvent and optionally water, or an aqueous solution, allows for combinations of gelators (such as GRAS amphiphiles or prodrug-based gelators), co-gelators (such as anti-retrovirals), and solvents to form self-supporting hydrogels or organogels. The resulting gels may be used in methods of treating HIV and/or hepatitis.

1 - 23 . (canceled) 
     
     
         24 . A formulation for oral administration comprising a self-assembled gel, the self-assembled gel comprising
 one or more gelators, wherein the one or more gelators are selected from ascorbyl palmitate, triglycerol monostearate, sucrose palmitate, alpha tocopherol acetate, cholesterol, lysophosphatidylcholine, sorbitan monostearate, retinyl acetate, retinyl palmitate, or mixtures thereof;   one or more organic solvents;   one or more co-solvents selected from water or an aqueous solution; and   one or more therapeutic, prophylactic, and/or diagnostic agents,   wherein the gelators form ordered lamellar, vesicular, and/or nanofibrous structures having the therapeutic, prophylactic and/or diagnostic agent physically entrapped, encapsulated, or non-covalently associated therewith.   
     
     
         25 . The formulation for oral administration of the gel of  claim 24 , wherein the one or more gelators are selected from the group consisting ascorbyl palmitate, triglycerol monostearate, sucrose palmitate, sorbitan monostearate, retinyl acetate, and retinyl palmitate. 
     
     
         26 . The formulation for oral administration of  claim 24 , wherein the one or more gelators is ascorbyl palmitate. 
     
     
         27 . The formulation for oral administration of  claim 24 , wherein the one or more gelators is triglycerol monostearate. 
     
     
         28 . The formulation for oral administration of  claim 24 , wherein the one or more organic solvents are selected from the group consisting of hexyl butyrate, glycerol, ethylene glycol, propylene glycol, dipropylene glycol, N-methyl-2-pyrrolidone (NMP), acetone, dimethylformamide (DMF), tetrahydrofuran, dioxane, acetonitrile, alcohols, benzene, toluene, carbon tetrachloride, acetonitrile, 1,4-dioxane, dimethyl sulfoxide (DMSO), chloroform, hexane, mesitylene, and combinations thereof. 
     
     
         29 . The formulation for oral administration of  claim 24 , wherein the one or more organic solvents are present in less than about 50%, about 40%, about 30%, about 25%, about 20%, about 15%, or about 10% by vol/vol of the total volume of the gel. 
     
     
         30 . The formulation for oral administration of  claim 24 , wherein the water is selected from the group consisting of distilled water, de-ionized water, pure water, and ultrapure water. 
     
     
         31 . The formulation for oral administration of  claim 24 , wherein the aqueous solution is selected from the group consisting of saline, phosphate buffered saline (PBS), Ringer's solution, and isotonic sodium chloride. 
     
     
         32 . The formulation for oral administration of  claim 24 , comprising one or more therapeutic, prophylactic, and/or diagnostic agents selected from the group consisting of proteins, anti-inflammatory agents, steroids, contraceptives, antibiotics, immunosuppressants, chemotherapeutics, sensitizing agents, immunomodulatory agents, antibody fragments, cytokines, cells, stem cells, siRNA, vitamins, and combination thereof. 
     
     
         33 . The formulation for oral administration of  claim 32 , comprising proteins selected from the group consisting of enzymes, antibodies, growth factors, antigens, and peptides. 
     
     
         34 . The formulation for oral administration of  claim 32 , comprising immunomodulatory agents selected from the group consisting of steroids, non-antiinflammatory agents, chemotherapeutics, anesthetics, analgesics, anti-pyretic agents, anti-infectious agents, antifungal agents, vitamins, therapeutic RNAs, microRNA, PiRNA, ribozymes, and nucleotides encoding proteins or peptides. 
     
     
         35 . The formulation for oral administration of  claim 24 , comprising diagnostic agents selected from the group consisting of paramagnetic molecules, fluorescent compounds, magnetic molecules, and radionuclides. 
     
     
         36 . The formulation for oral administration of  claim 24 , comprising particles of the self-assembled gel. 
     
     
         37 . The formulation for oral administration of  claim 36 , wherein the formulation is a suspension. 
     
     
         38 . The formulation for oral administration of  claim 24 , wherein the self-assembled gel is a xerogel. 
     
     
         39 . The formulation for oral administration of  claim 38 , wherein the xerogel is a powder.