Carboplatin-liposomes (CPL) in immunodeficient mice: improved antitumor activity for breast carcinomas and stimulation of hematopoiesis.
Carboplatin-liposomes (CPL) have been shown to possess a strong stimulatory activity on the hematopoiesis in immunocompetent mice. As we were interested in studying this pharmacological characteristic in parallel with any antitumour effects which might be expected for the encapsulated cytostatic, we used a panel of six human breast carcinomas xenotransplanted to nude mice. The antitumor activity as well as the hematopoietic effects of the vesicles were studied in comparison to, and in combination with, the free drug. Carboplatin was encapsulated into reverse phase evaporation vesicles (REV) and injected i.p. as a single dose of 75 mg kg-1 into tumor-free and breast-carcinoma-bearing animals, respectively. Following a single application of CPL in nude mice, a significant increase of the WBC numbers to about three times for that of the normal level could be observed over a period of at least 28 days. The elevation was due to an increase in both circulating granulocytes and lymphocytes. The peripheral effect was accompanied by a relative decrease of spleen cellularity, while the number of bone marrow cells was hardly affected. There was no influence detectable on circulating blood cells in SCID mice. However, a rather high toxicity of CPL for this immunodeficient mouse strain was noticed. In the panel of breast carcinomas used, free carboplatin and CPL displayed a different pattern of therapeutic efficiencies. In four of the five tumor models tested, a combination of the free with the liposomal drug showed a significant inhibition of tumor growth while effectively preventing a drug-induced leukopenia.(ABSTRACT TRUNCATED AT 250 WORDS)
Fichtner
I
I
Max-Delbrück-Center of Molecular Medicine, Berlin, Germany.
Reszka
R
R
Goan
S R
SR
Naundorf
H
H
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D016190:Carboplatin / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D004337:Drug Carriers; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016867:Immunocompromised Host; D008081:Liposomes; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011960:Receptors, Estrogen / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008081:Liposomes; D011960:Receptors, Estrogen; D016190:Carboplatin