Intravenous liposomal benznidazol as trypanocidal agent: increasing drug delivery to liver is not enough

M.J. MORILLA, J. A. MONTANARI, M.J. PRIETO, M.O. LOPEZ, P.B. PETRAY AND E.L. ROMERO.

INTERNATIONAL JOURNAL OF PHARMACEUTICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2004 vol. 278 p. 311 - 318

0378-5173

With the aim of investigating if delivery of benznidazole (BNZ) to liver could be increased by incorporating the drug in multilamellar liposomes, single bolus of free BNZ or liposomal BNZ formulations (MLV-BNZ) composed of HSPC:DSPG:Chol 2:1:2 (mol/mol/mol) at 0.7% (w/w) drug/total lipid ratio, were injected by intramuscular (i.m.), subcutaneous (s.c.) and intravenous(i.v.) routes, at 0.2 mg BNZ/kg, in rats. The resulting blood concentrations were followed along 9 h post-injection (p.i.) and drug accumulation in liver was determined after 4 and 9 h p.i. Only upon i.v. injection of MLV-BNZ, a threefold higher BNZ accumulation in liver was obtained, together with blood BNZ concentrations of 1.1g/ml (30% lower than the blood BNZ concentrationachieved upon i.v. administration of free drug) occurred 4 h p.i. However, such increased liver uptake of BNZ, raised twice a week had no effect on parasitaemia levels of mice infected with the RA strain of Trypanosoma cruzi. Our results indicate that the relationship between increased selectivity for an infected tissue and therapeutic effect is not always straightforward, at leastfor the MLV-BNZ regimen used in the present study.