Controlled Release Formulations

Abstract

The present invention provides stable, self-assembling, biocompatible and biodegradable hydrogel formulations, into which one or more compounds may be incorporated allowing for delayed release or controlled release of the incorporated compounds as the hydrogel is degraded in the body.

What is claimed is: 
     
         1 . A controlled release formulation comprising a therapeutic agent entrapped in an alkyglycoside biodegradable hydrogel. 
     
     
         2 . The controlled release formulation of  claim 1 , wherein the therapeutic agent is methotrexate. 
     
     
         3 . The controlled release formulation of  claim 1 , wherein the therapeutic agent is folic acid. 
     
     
         4 . The controlled release formulation of  claim 1 , wherein the therapeutic agent is curcumin. 
     
     
         5 . The controlled release formulation of  claim 4 , further comprising sodium bicarbonate. 
     
     
         6 . The controlled release formulation of  claim 1 , wherein alkylglycoside is tetradecylmaltoside. 
     
     
         7 . A controlled release formulation comprising a therapeutic agent entrapped in a sucrose ester biodegradable hydrogel. 
     
     
         8 . The controlled release formulation of  claim 7 , wherein the therapeutic agent is methotrexate. 
     
     
         9 . The controlled release formulation of  claim 7 , wherein the therapeutic agent is folic acid. 
     
     
         10 . The controlled release formulation of  claim 9 , further comprising sodium bicarbonate. 
     
     
         11 . The controlled release formulation of  claim 7 , wherein the therapeutic agent is curcumin. 
     
     
         12 . The controlled release formulation of  claim 7 , wherein the sucrose stearate is a sucrose stearate. 
     
     
         13 . A controlled release bilayer formulation comprising a first layer and a second layer, wherein the first layer comprises a first therapeutic agent entrapped in a alkylglycoside biodegradable hydrogel, and the second layer comprises a second therapeutic agent entrapped in a sucrose ester biodegradable hydrogel. 
     
     
         14 . The controlled release bilayer formulation of  claim 13 , wherein the first layer comprises a first therapeutic agent entrapped in a tetradecylmaltoside biodegradable hydrogel, and the second layer comprises a second therapeutic agent entrapped in a sucrose stearate biodegradable hydrogel 
     
     
         15 . The controlled release bilayer formulation of  claim 13 , wherein the first therapeutic agent is methotrexate. 
     
     
         16 . The controlled release bilayer formulation of  claim 13 , wherein the second therapeutic agent is folic acid. 
     
     
         17 . The controlled release bilayer formulation of  claim 13 , wherein the first therapeutic agent is methotrexate and the second therapeutic agent is folic acid. 
     
     
         18 . A method of treating rheumatoid arthritis comprising administering to a subject in need thereof a therapeutically effective amount of a controlled release bilayer formulation, wherein the formulation comprises a first layer and a second layer, wherein the first layer comprises methotrexate entrapped in a tetradecylmaltoside biodegradable hydrogel, and the second layer comprises folic acid entrapped in a sucrose stearate biodegradable hydrogel. 
     
     
         19 . A method for increasing the residency time of a therapeutic agent during intranasal or pulmonary delivery of the agent to a subject, comprising applying to the nasal or pulmonary mucosa of the subject a composition comprising:
 a) an alkylglycoside or sucrose ester;   b) an acetate buffer; and   c) a therapeutic agent,   thereby increasing the residency time of the therapeutic agent in the nasal or pulmonary mucosa.   
     
     
         20 . A hydrogel comprising:
 a) methotrexate;   b) an alkylglycoside or sucrose ester; and   c) an aqueous buffer.   
     
     
         21 . A method for treating arthritis in a subject in need thereof comprising administering to the skin of the subject at a location proximal to an affected area the hydrogel of  claim 20 . 
     
     
         22 . The method of  claim 21 , wherein the methotrexate is administered at a concentration of about 3% w/w. 
     
     
         23 . A method for treating arthritis comprising administering nasal or pulmonary mucosa of a subject in need thereof the hydrogel of  claim 20 , thereby avoiding the first pass effect of the liver. 
     
     
         24 . The method of  claim 23 , wherein the methotrexate is administered at a concentration of about 3% w/w. 
     
     
         25 . A hydrogel comprising:
 a) methylene blue;   b) an alkylglycoside or sucrose ester; and   c) an aqueous buffer.   
     
     
         26 . A method for treating Alzheimer's disease comprising administering to an affected area of skin of a subject in need thereof the hydrogel of  claim 25 . 
     
     
         27 . The method of  claim 26 , wherein the methylene blue is administered at a dosage of 30 mg, 60 mg, or 120 mg.