Method of administration and treatment

Abstract

Provided herein are formulations for topical and/or transdermal administration, and methods of using these formulations for the treatment of proliferative diseases related to cancer such as cancers and related conditions, and solid minors. Also provided are formulations for topical and/or transdermal administration, and methods of using these formulations for melasma, gout, skin disorders, and other diseases and disorders described herein as well as methods for modulating the pH (e.g. raising) of a tissue or microenvironment proximal to a tumor, modulating pH, or improving the effectiveness of know chemotherapeutic agents, immunotherapy and the like for the prevention, treatment of cancers and related conditions described herein.

1 . A method of treating a proliferative disorder associated with cancer in a patient, the method comprising administering an effective amount of a formulation for transdermal delivery through the skin of a subject comprising one or more buffering agent to a patient in need thereof, wherein said administration is effective to i) inhibit or prevent the growth of a tumor or tumor cells, ii) inhibit or prevent the metastasis of tumors or cancer cells, iii) inhibit or prevent carcinogenesis, iv) inhibit or prevent the intravasation of tumor cells, or v) improve or extend the duration of remission, or maintain remission of a cancer or tumor. 
     
     
         2 . A method according to  claim 1 , wherein said treating a proliferative disorder inhibits or prevents the growth of a tumor or tumor cells. 
     
     
         3 . A method according to  claim 1 , wherein said treating a proliferative disorder inhibits or prevents the metastasis of tumors or cancer cells. 
     
     
         4 . A method according to  claim 1 , wherein said treating a proliferative disorder inhibits or prevents carcinogenesis. 
     
     
         5 . A method according to  claim 1 , wherein said treating a proliferative disorder inhibits or prevents the intravasation of tumor cells. 
     
     
         6 . A method according to  claim 1 , wherein said treating a proliferative improves or extends the duration of remission or maintains remission of a cancer or tumor. 
     
     
         7 . A method of treating cancer in a patient, the method comprising administering an effective amount of a formulation for transdermal delivery through the skin of a subject comprising one or more buffering agent to a patient in need thereof, wherein said administration is effective to inhibit or prevent the growth of a tumor or tumor cells. 
     
     
         8 . A method of preventing metastasis of tumors, the method comprising administering an effective amount of a formulation for transdermal delivery through the skin of a subject comprising one or more buffering agent to a patient in need thereof, wherein said administration is effective to inhibit or prevent the metastasis of tumors or cancer cells. 
     
     
         9 . A method according to  claim 1 , wherein said formulation for transdermal delivery through the skin of a subject comprises a buffering agent comprising a carbonate salt in an amount between about 10-56% w/w; a penetrant portion in an amount between about 5 to 55% w/w; a detergent portion in an amount of at least 1% w/w; and wherein the formulation comprises water in an amount from 0% w/w up to 70% w/w, and wherein the formulation optionally comprises lecithin in an amount less than about 12% w/w. 
     
     
         10 . A method according to  claim 1 , wherein said formulation for transdermal delivery through the skin of a subject comprises a buffering agent comprising at least one carbonate salt, lysine, tris, a phosphate buffer and/or 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA), or a combination thereof in an amount between about 10-56% w/w; and a penetrant portion in an amount between about 44 to 90% w/w, wherein the penetrant portion comprises water in an amount less than about 85% w/w, and wherein the formulation comprises less than about 12% w/w lecithin. 
     
     
         11 . A method according to  claim 10 , wherein a chemotherapeutic or immunotherapeutic agent is co-administered with said formulation comprising one or more buffering agent. 
     
     
         12 . A method according to  claim 10 , wherein said administration is effective to alter the pH of a tissue or microenvironment proximal to a solid tumor or cancer cells in the patient. 
     
     
         13 . A method according to  claim 11 , wherein the chemotherapeutic or immunotherapeutic agent is selected from alkylating agents, antibodies and related binding proteins, anthracyclines, antimetabolites, antitumor antibiotics, aromatase inhibitors, taxanes and related compounds, cytoskeletal disruptors, epothilones, histone deacetylace inhibitors, kinase inhibitors, nucleoside analogues, topoisomerase inhibitors, retinoids, and vinca alkaloids and derivatives thereof. 
     
     
         14 . A method according to  claim 13 , wherein the chemotherapeutic or immunotherapeutic agent is an immunotherapeutic agent selected from alemtuzumab, atezolizumab, avelumab, ipilimumab, durvalumab, nivolumab, ofatumumab, rituximab and trastuzumab. 
     
     
         15 . A method according to  claim 10 , comprising a carbonate salt in an amount between about 7-56% w/w of the formulation. 
     
     
         16 . A method according to  claim 15 , wherein the carbonate salt in said formulation is in an amount between about 15-32% w/w of the formulation. 
     
     
         17 . A method according to  claim 15 , wherein the carbonate salt in said formulation is sodium carbonate and/or sodium bicarbonate milled to a particle size is less than 200 μm. 
     
     
         18 . A method according to  claim 15 , wherein the penetrant component in said formulation is in an amount between about 18-42% w/w of the formulation. 
     
     
         19 . A method according to  claim 15 , wherein the water in said formulation is in an amount between about 15-42% w/w of the formulation. 
     
     
         20 . A method according to  claim 15 , wherein the penetrant portion in said formulation comprises an alcohol in an amount less than 5% w/w of the formulation.