Hydrophobic photosensitizer formulations for photodynamic therapy

Abstract

Pharmaceutical liposomal formulations for photodynamic therapy are presented, which are stable in storage as liquid formulations, comprise a hydrophobic photosensitizer and one or more synthetic phospholipids. The liposomal formulations provide therapeutically effective amounts of the photosensitizer for intravenous administration. The formed liposomes contain the hydrophobic photosensitizer within the lipid bilayer membrane. In the present formulation the size of the liposomal vehicles and their content of a therapeutically effective amount of the photosensitizing agent remain unchanged over storage times of a year or more, thus making the liquid formulations commercially viable. Being stable in the liquid state also makes them easy to store, and easier to use for doctors and patients. They can be prepared in a ‘factory setting’ delivered to practitioners in a liquid state and be available for use in PDT related treatments as called for by the practitioners' patient needs.

1 . A pharmaceutical liposomal formulation for photodynamic therapy, which is stable without freeze-drying, comprising: 
 a liposomal bilayer which consists substantially of two or more synthetic phospholipids; and,    a therapeutically effective amount of a hydrophobic photosensitizer, contained within said liposomal bilayer.    
     
     
         2 . The liposomal formulation according to  claim 1 , wherein said synthetic phospholipids are selected from the group consisting of dipalmitoyl phosphatidyl choline, distearoyl phosphatidyl choline, dipalmitoyl phosphatidyl glycerol, distearoyl phosphatidyl glycerol. and combinations of these materials.  
     
     
         3 . The liposomal formulation according to  claim 1 , wherein said synthetic phospholipids are a combination of dipalmitoyl phosphatidyl choline and dipalmitoyl phosphatidyl glycerol.  
     
     
         4 . The liposomal formulation according to  claim 3 , wherein the weight ratio of said phosphatidyl choline to said phosphatidyl glycerol is about 10:1.  
     
     
         5 . The liposomal formulation according to  claim 1 , wherein said hydrophobic photosensitizer is selected from the group consisting of pheophorbide and dihydro and tetrahydro porphyrin compounds.  
     
     
         6 . The liposomal formulation according to  claim 5 , wherein said hydrophobic photosensitizer is temoporfin.  
     
     
         7 . The liposomal formulation according to  claim 1 , wherein said therapeutically effective amount of the photosensitizer is from 0.0001 to 0.15 percent w/v.