A study of the potential application of bleomycin entrapped within liposomes in the treatment of human cerebral gliomas.

Human cerebral gliomas are the most commonly occurring form of brain tumour, yet treatment has only a marginal effect on the outcome, with poorly differentiated gliomas having a mean survival time of between six months and one year. In view of the large kinetic difference in cell division-rates of the tumour and normal brain tissue, chemotherapy might be expected to be effective in the treatment of this condition, yet the blood-brain barrier prevents the delivery of most chemotherapeutic agents at therapeutic concentrations to the tumour following systemic administration. Local injection of drug into the tumour has been attempted, but the vascularity of the glioma tissue bed is such that sufficiently high concentrations of drug cannot be sustained for an adequate period of time. An inert depot preparation of the drug injected locally, giving sustained release of drug at therapeutic concentrations, might be more effective and therefore an investigation has been made of the use of liposomes containing high concentrations of bleomycin as a means of achieving this goal. By careful study of the factors affecting incorporation of drugs within liposomes, high entrapment efficiencies of bleomycin have been achieved and these preparations have been shown to have similar dose-response curves against a glioma cell line as free preparations of the drug. Following intracerebral injection of bleomycin entrapped within liposomes in rats , no detectable cerebral toxicity could be demonstrated, and a delayed clearance of the drug from the injection site occurred as compared with local injection of similar concentrations of free bleomycin. Liposome-bleomycin preparations, when injected through Ommaya reservoirs into the residual tumour bed of patients with grade IV cerebral gliomas following surgery, were well tolerated with only minimal side effects being observed. Only very low concentrations of bleomycin appeared in the blood, and urinary clearance of the drug was considerably reduced as compared to when free drug was injected via the reservoir. These preliminary observations suggest a role for the local delivery of drugs entrapped within liposomes in the treatment of human cerebral gliomas