Pegylated liposomal formulations of hydrophobic photosensitizers for photodynamic therapy

摘要

Pharmaceutical pegylated liposomal formulations for photodynamic therapy are presented. The pegylated liposomal formulation provides therapeutically effective amounts of the photosensitizer for intravenous administration. At least one of the phospholipids in the liposomes has been linked with poly ethylene glycol (PEG) as an integral part of the phospholipids. The formed pegylated liposomes contain the hydrophobic photosensitizer within the lipid bilayer membrane. Pegylation of liposomes carrying the hydrophobic photosensitizer helps to maintain the drug level within the therapeutic window for longer time periods and provides the drug a longer circulating half life in vivo. Further the pegylated formulation of hydrophobic photosensitizers shows improved pharmacokinetics over standard non-liposomal formulations thus enhancing the efficacy of PDT with the pegylated liposomal formulations.

主权项

1. A pharmaceutical liposomal formulation for photodynamic therapy, the liposomal formulation comprising:
a liposomal bilayer, said bilayer consisting essentially of synthetic phospholipids, wherein said synthetic phospholipids are a combination of dipalmitoyl phosphatidyl choline, dipalmitoyl phosphatidyl glycerol and pegylated distearoyl phosphatidyl ethanolamine; and a therapeutically effective amount of temoporfin contained within said liposomal bilayer,
wherein the weight ratio of the dipalmitoyl phosphatidyl choline to the dipalmitoyl phosphatidyl glycerol is 10:1;the weight ratio of the dipalmitoyl phosphatidyl choline to the pegylated distearoyl phosphatidyl ethanolamine is from 10:1 to 5:1; andthe liposomal formulation is stable for at least four months at about 23° C. without freeze-drying.