Liposomes containing a cisplatin compound

DETAILED DESCRIPTION In one aspect, the invention includes a liposomal composition containing an entrapped cisplatin compound.
The composition includes liposomes having an outer surface and an inner surface defining an aqueous liposome compartment.
The liposomes are composed of a vesicle-forming lipid and between about 1-20 mole percent of a vesicle-forming lipid derivatized with a hydrophilic polymer.
The liposomes are formed such that the hydrophilic polymer forms a coating of hydrophilic polymer chains on both the inner and outer surfaces.
The cisplatin compound is entrapped in the liposomes with substantially greater retention than in liposomes lacking the inner and outer polymer surface coatings.
The cisplatin compound, in one embodiment, is native cisplatin and is entrapped in the liposomes at a drug-to-lipid ratio of between about 10 to 20 .
mu.
g/mg total lipid.
In another embodiment, the cisplatin compound is a cisplatin analogue.
In another embodiment, the hydrophilic polymer chains are composed of a hydrophilic polymer selected from the group consisting of polyvinylpyrrolidone, polyvinylmethylether, polymethyloxazoline, polyethyloxazoline, polyhydroxypropyloxazoline, polyhydroxypropylmethacrylamide, polymethacrylamide, polydimethylacrylamide, polyhydroxypropylmethacrylate, polyhydroxyethylacrylate, hydroxymethylcellulose, hydroxyethylcellulose, polyethyleneglycol, and polyaspartamide.
In a preferred embodiment, the hydrophilic polymer is polyethyleneglycol.
The liposomes, in one embodiment have sizes between about 80-160 nm, preferably 100-140 nm, most preferably between about 100-120 nm.
In a preferred embodiment, the vesicle forming lipid is hydrogenated soy phosphatidylcholine and the derivatized vesicle forming lipid is distearyl phosphatidylethanolamine derivatized with polyethylene glycol.
In another aspect, the invention includes a method of entrapping a cisplatin compound in liposomes, by heating an aqueous solution of a cisplatin compound to a temperature sufficient to increase its solubility over the compound's solubility at room temperature