Diblock copolymer and use thereof in a micellar drug delivery system

Abstract

The present invention relates to diblock copolymers and more particularly to polycaprolactone-b-polyethylene oxide (PCL-b-PEO) diblock copolymers used in micellar systems, for delivering a biologically active agent to a site There is provided a diblock copolymer compound comprising a hydrophilic block and a hydrophobic block, the hydrophilic block comprising a polyethylene oxide (PEO) polymer, the hydrophobic block comprising a polycaprolactone (PCL) polymer, the PCL polymer comprising a number of caprolactone monomers selected from 5 to 150, the PEO polymer comprising a number of ethylene oxide monomers selected from 30 to 100. The diblock copolymer compound of the present invention may be used to form a micellar delivery system for delivering biologically active agents such as lipophilic drugs to sites such as the central nervous system. The hydrophobic reservoir obtained enables a larger amount of agent to be incorporated therein, with a slower release and without the damaging effects that such high doses would induce with known delivery systems.

What is claimed is:  
     
         1 . A diblock copolymer comprising a hydrophilic block and a hydrophobic block, said hydrophilic block comprising a polyethylene oxide polymer, said hydrophobic block comprising a polycaprolactone polymer, said polycaprolactone polymer comprising a number of caprolactone monomers selected from 5 to 150, said polyethylene oxide polymer comprising a number of ethylene oxide monomers selected from 20 to 100, wherein said diblock copolymers are assembled in a suitable aqueous medium such that said hydrophobic blocks define a core of said micellar system and said hydrophilic blocks define a shell surrounding said core.  
     
     
         2 . The diblock copolymer micellar system according to  claim 1 , wherein said number of caprolactone monomers is 20 and said number of ethylene oxide monomers is 44; wherein said diblock copolymers are assembled in a suitable aqueous medium such that said hydrophobic blocks define a core of said micellar system and said hydrophilic blocks define a shell surrounding said core.  
     
     
         3 . A diblock copolymer comprising a hydrophilic block and a hydrophobic block, said hydrophilic block comprising a polyethylene oxide polymer, said hydrophobic block comprising a polycaprolactone polymer, said polycaprolactone polymer comprising 20 caprolactone monomers, said polyethylene oxide polymer comprising 44 ethylene oxide monomers, wherein said diblock copolymers are assembled in a suitable aqueous medium such that said hydrophobic blocks define a core of said micellar system and said hydrophilic blocks define a shell surrounding said core.  
     
     
         4 . A diblock copolymer micellar system according to  claim 1 , wherein said micellar system has a diameter varying essentially from about 10 nanometers to about 100 nanometers.  
     
     
         5 . A diblock copolymer micellar system according to claim 2, wherein said micellar system has a diameter varying essentially from about 10 nanometers to about 100 nanometers.  
     
     
         6 . A diblock copolymer micellar system according to anyone of  claim 2 , wherein said micellar system contains a biologically active agent into said core.  
     
     
         7 . A diblock copolymer micellar system according to  claim 3 , wherein said biologically active agent is lipophilic.  
     
     
         8 . A diblock copolymer micellar system according to  claim 4 , wherein said biologically active agent comprises a neuroactive agent.  
     
     
         9 . A diblock copolymer micellar system according to  claim 5 , wherein said neuroactive agent is a neurotrophic agent selected from the group consisting of FK506 and L-685,818.  
     
     
         10 . A diblock copolymer micellar system according to  claim 6 , wherein said neuroactive agent consists of L-685,818.  
     
     
         11 . A composition comprising a population of micellar systems according to  claim 3  in combination with a suitable pharmaceutical carrier.  
     
     
         12 . A composition comprising a population of micellar systems according to  claim 7  in combination with a suitable pharmaceutical carrier.  
     
     
         13 . A composition according to  claim 7 , wherein said copolymers are present in a solution in an amount of about 1 percent by weight.  
     
     
         14 . A delivery system for delivering a biologically active agent in situ in a patient, the delivery system comprising a population of micellar systems according to  claim 1 .  
     
     
         15 . A delivery system according to  claim 11 , wherein said in situ delivery is to the central nervous system of said patient.  
     
     
         16 . A method for preparing a population of micellar systems according to  claim 1  which comprises the steps of: 
 a) dissolving said copolymers in a suitable organic solvant solution; and  
 b) adding water in a dropwise fashion to said solution to form said micellar systems.