Micellar drug delivery systems for hydrophobic drugs

Abstract

This invention provides compositions comprising a hydrophobic drug, a biocompatible micelle forming polymer, and a biocompatible low molecular weight, water-soluble polymer. Also provided are devices for injection of such compositions and for the use of such compositions to form hydrophobic drug containing micelles within the body of a patient.

1 . A micelle forming composition comprising: 
 (a) one or more hydrophobic drugs;    (b) one or more biocompatible, micelle forming polymers; and,    (c) one or more biocompatible, low molecular weight, water soluble polymers,    wherein the one or more water soluble polymers are present in an amount sufficient that the composition is injectable.    
     
     
         2 . The composition of  claim 1 , wherein the composition is substantially free of non-polymeric organic solvent.  
     
     
         3 . The composition of  claim 1 , wherein the one or more micelle forming polymers comprises a block copolymer.  
     
     
         4 . The composition of  claim 3 , wherein the block copolymer comprises a hydrophobic portion comprising a polymer block selected from the group consisting of: a polyester and a polyanhydride.  
     
     
         5 . The composition of  claim 4 , wherein the block copolymer is selected from the group consisting of: polyglycolic acid, polybutrylactone, polyhydroxybutyrate, polylactic acid and polycaprolactone.  
     
     
         6 . The composition of  claim 4 , wherein the hydrophobic portion of the block copolymer having a molecular weight of about 200 to about 500.  
     
     
         7 . The composition of  claim 3 , wherein the block copolymer further comprises a hydrophilic portion that is a polyethylene oxide.  
     
     
         8 . The composition of  claim 7 , wherein the polyethylene oxide is selected from the group consisting of polyethylene glycol (PEG) and methoxypolyethylene glycol (MePEG).  
     
     
         9 . The composition of  claim 7 , wherein the hydrophilic portion is a polymer having a molecular weight of at least 750 and less than about 8000.  
     
     
         10 - 14 . (canceled).  
     
     
         15 . The composition of  claim 1 , wherein the water-soluble polymer is selected from the group consisting of: a polyethylene oxide, low molecular weight polylactic acid, low molecular weight polyglycolic acid and a pluronic, wherein the water soluble polymer is a liquid or semi-solid at room temperature.  
     
     
         16 . The composition of  claim 15 , wherein the water soluble polymer is a polyethylene oxide.  
     
     
         17 . The composition of  claim 16 , wherein the polyethylene oxide is selected from the group consisting of PEG and MePEG.  
     
     
         18 . The composition of  claim 17 , wherein the polyethylene oxide has a molecular weight of about 1000 or less.  
     
     
         19 . A device for injection of a substance into the body of a patient wherein the device comprises a composition of  claim 1  for injection.  
     
     
         20 . The device of  claim 19 , wherein the device is a syringe.  
     
     
         21 . The device of  claim 20 , wherein the syringe further comprises a needle cannula.  
     
     
         22 - 25 . (canceled).  
     
     
         26 . A micelle forming composition comprising: 
 (a) one or more hydrophobic drugs;    (b) one or more biocompatible, micelle-forming polymers; and, (c) one or more biocompatible, low molecular weight, water soluble polymers,    wherein the micelle-forming polymer is a block copolymer comprising a hydrophobic and a hydrophilic portion, and wherein the hydrophilic portion is a polyethylene oxide having a molecular weight of about 750 or more.    
     
     
         27 . The composition of  claim 26 , wherein the hydrophobic portion comprises a block copolymer selected from the group consisting of: polyester, polyanhydride, polyglycolic acid, polybutrylaction, polyhyrdroxybutyrate, polylactic acid and polylacaprolactone.  
     
     
         28 . The composition of  claim 27 , wherein the hydrophobic portion is a polymer having a molecular weight of about 200 to about 500.  
     
     
         29 . The composition of  claim 26 , wherein the water soluble polymer is a water soluble, low molecular weight, polylactic or polyglycolic acid; a water soluble pluronic polymer; or, a polyethylene oxide, wherein the water soluble polymer is a liquid or semi-solid at room temperature.  
     
     
         30 . The composition of  claim 29 , wherein the water soluble polymer is a polyethylene oxide having a molecular weight of about 1000 or less selected from the group consisting of PEG and MePEG.  
     
     
         31 . The composition of  claim 26 , wherein the amount of water soluble polymer in the composition is sufficient for the composition to be injectable.  
     
     
         32 . The composition of  claim 26 , wherein the composition is substantially free of organic solvent.  
     
     
         33 . The composition of  claim 26 , wherein the composition is capable of forming micelles in aqueous medium at a critical micelle concentration (CMC) of about 500 μM or less.  
     
     
         34 .- 35 . (canceled).  
     
     
         36 . A method of forming micelles comprising a hydrophobic drug, wherein a composition according to any one of  claim 1  is placed in an aqueous media whereby micelles comprising the hyrdrophobic drug are formed therein.  
     
     
         37 . The method of  claim 36 , wherein said placing is in vitro.  
     
     
         38 . The method of  claim 36 , wherein said placing is in vivo.  
     
     
         39 .- 40 . (canceled)