Studies on the intracerebral injection of bleomycin free and entrapped within liposomes in the rat.

Reverse phase prepared liposomes of defined composition (dipalmitoyl phosphatidyl choline, cholesterol and dipalmitoyl phosphatidic acid; 7:2:1; DPC) when injected intracerebrally in the rat produced no tissue damage beyond that of the penetrating wound, or altered behaviour pattern over 1 week of observation. The cerebral tissue response and behaviour of rats injected with bleomycin of increasing concentration, free and entrapped within liposomes was studied in short and long term experiments. In separate experiments blood, urine and tissue levels of bleomycin were measured after intracerebral injection of free and liposome entrapped bleomycin in the rat. These studies demonstrated that bleomycin when entrapped within liposomes and injected intracerebrally was of low toxicity to normal cerebral tissue, and was cleared more slowly from the injection site than when the free drug was injected. The results obtained indicated a potential application for drugs entrapped within liposomes acting as a depot preparation in the treatment of cerebral gliomas.