Antineoplastic activity and toxicity of some alkylating cytostatics (Cyclophosphamide, CCNU, Cytostasan) encapsulated in liposomes in different murine tumour models

Abstract

The encapsulation of Cyclophosphamide in MLV (PC : CH 1:1) revealed a total loss of antineoplastic activity in the P 388 tumour model compared to an equal dose of the free drug, though a moderate toxicity, registered as decrease of leukocyte and platelet counts, was still present. CCNU in liposomes of different size and composition showed in lower doses a diminished therapeutic effectiveness in the P388 or L1210 leukaemia and the B 16 melanoma, while in higher doses toxic deaths occurring with the free drug could be prevented totally by using liposomes. Liposomal encapsulation also influenced body weight change and leukocyte counts, causing them to be less drastically reduced than with use of the free drug. The entrapment of Cytostasan, an N-lost derivative, had the same effect on the increase of lifespan of tumour-bearing animals (mammary carcinoma 1142 A) as equal doses of the free drug and caused only a slight improvement of toxicity. In general, liposomal encapsulation of alkylating cytostatics seems advantageous only for certain lipophilic drugs.