Intra-tumoral injection of doxorubicin (adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated withlocal 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 cardiotoxi city. However, it does not always enhance anti-tumor effects because of ent rapment by the reticuloendothelial system, In this study, we investigated t he 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 establi shed 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. H istological examination showed no tissue damage at the site of s.c, injecti on of LipADM, ADM concentrations in tumor tissues after intra-tumoral injec tion were persistently high in the LipADM-treated group. Our results indica te 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. (C) 2000 Wiley-Liss, Inc.