INVESTIGADORES
MORILLA Maria Jose
artículos
Título:
Etanidazole in pH-sensitive liposomes: Design, characterization
Autor/es:
MARIA JOSE MORILLA, JORGE MONTANARI, FERNANDA FRANK, EMILIO MALCHIODI, RICARDO CORRAL, PATRICIA PETRAY, EDER LILIA ROMERO
Revista:
JOURNAL OF CONTROLLED RELEASE
Editorial:
Elsevier
Referencias:
Lugar: Amsterdam; Año: 2005 vol. 103 p. 599 - 607
ISSN:
0168-3659
Resumen:
In this work, the hydrophilic, low molecular weight and trypanocidal drug etanidazole (ETZ) was loaded in pH-sensitive
liposomes (L-ETZ). Liposomes were made of dioleoyl-phosphatidylethanolamine: cholesteryl hemisuccinate (DOPE:CHEMS,
6:4, mol:mol), of 380 nm size at 14% ETZ/total lipid (w/w) ratio. To follow their uptake and intracellular fate by fluorescence
microscopy, pH-sensitive liposomes were loaded with the fluorophore/quencher pair HPTS/DPX. A fast and massive delivery
of the liposomal aqueous content into the cytosol of murine J774 macrophages was observed. L-ETZ vesicles were
phagocytosed by both uninfected and Trypanosoma cruzi-infected macrophages. A 72% of anti-amastigote activity (AA) was
demonstrated on L-ETZ-treated J774 cells, whereas the same dose of free ETZ rendered 0% AA. Endovenous administration of
L-ETZ at 14 Ag/mouse dose provoked significant decrease in parasitemia levels of T. cruzi-infected mice. Conversely,
inoculation of a 180-fold higher dose of free ETZ failed in reducing the number of bloodstream trypomastigotes. Hence, these
results point to develop systems, such as L-ETZ, designed for selective delivery of drugs to the cytoplasm of phagocytic cells,
thus enhancing the efficacy of molecules considered poorly activeTrypanosoma cruzi-infected macrophages. A 72% of anti-amastigote activity (AA) was
demonstrated on L-ETZ-treated J774 cells, whereas the same dose of free ETZ rendered 0% AA. Endovenous administration of
L-ETZ at 14 Ag/mouse dose provoked significant decrease in parasitemia levels of T. cruzi-infected mice. Conversely,
inoculation of a 180-fold higher dose of free ETZ failed in reducing the number of bloodstream trypomastigotes. Hence, these
results point to develop systems, such as L-ETZ, designed for selective delivery of drugs to the cytoplasm of phagocytic cells,
thus enhancing the efficacy of molecules considered poorly activeAg/mouse dose provoked significant decrease in parasitemia levels of T. cruzi-infected mice. Conversely,
inoculation of a 180-fold higher dose of free ETZ failed in reducing the number of bloodstream trypomastigotes. Hence, these
results point to develop systems, such as L-ETZ, designed for selective delivery of drugs to the cytoplasm of phagocytic cells,
thus enhancing the efficacy of molecules considered poorly active