Intra-tumoral injection of doxorubicin (adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated with local or systemic side effects.
Encapsulation of doxorubicin (Adriamycin) in liposome (LipADM) augments the anti-tumor effects of the drug and reduces side effects such as cardiotoxicity. However, it does not always enhance anti-tumor effects because of entrapment by the reticuloendothelial system. In this study, we investigated the anti-tumor effect of LipADM injected directly into the tumor to augment tumor targeting. LipADM (7.5 mg/kg body weight), the same concentration as free ADM (FADM), was injected percutaneously or i.v. into 7-day-old established Meth-A tumors in mice. Mock liposome was injected percutaneously into tumors of control mice. Mean relative tumor weights of the 5 groups on day 15 were as follows: intra-tumoral injection of LipADM, 2.92 +/- 1.09; intra-tumoral injection of FADM, 6.99 +/- 2.92; i.v. injection of LipADM, 11.07 +/- 7.95; i.v. injection of FADM, 11.80 +/- 6.55; control, 23.94 +/- 9.03. Mean survival times were as follows: intra-tumoral injection of LipADM, 46.2 +/- 11.0 days; FADM, 34.6 +/- 9.6 days; mock control, 30.2 +/- 4.8 days. Histological examination showed no tissue damage at the site of s.c. injection of LipADM. ADM concentrations in tumor tissues after intra-tumoral injection were persistently high in the LipADM-treated group. Our results indicate that direct injection of LipADM into the tumor is therapeutically useful by producing persistently high concentrations of ADM in the target tissue, with few local and systemic side effects.
Idani
H
H
First Department of Surgery, Okayama University Medical School, Okayama, Japan.
Matsuoka
J
J
Yasuda
T
T
Kobayashi
K
K
Tanaka
N
N
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D007267:Injections; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin