Anti-leishmanial activity of a new formulation of amphotericin B.
The effectiveness of albumin microspheres loaded with amphotericin B was tested in an in vivo model of visceral leishmaniasis using the golden hamster. Free and encapsulated amphotericin B was tested at the dose of 1 mg/kg given by the intracardiac route on days 25, 26 and 27 post-infection (p.i.) to treat animals previously infected with 10(7) stationary promastigotes by the intracardiac route. Encapsulated amphotericin was highly effective against infection causing a reduction of 88.8% and 87.2% in the early stage of infection (day 32 p.i.) and of 66.7% and 54% in a later stage of infection (day 135 p.i.) in liver and spleen parasite load respectively, compared with untreated animals, whereas free amphotericin was inactive. Lymphocyte proliferation was restored together with an increase in CD4(+) subsets in animals treated with encapsulated amphotericin B, but not in those treated with the non-encapsulated compound. Antibody responses did not increase after treatment with encapsulated amphotericin B with antibody levels remaining at base levels for most animals in contrast to those of untreated or treated with free amphotericin, where in most animals the antibody levels sharply increased. This new formulation could be a more economical alternative to liposomes for the treatment of visceral leishmaniasis with amphotericin B.
Dea-Ayuela
M A
MA
Departamento de Parasitología, Universidad Complutense, Madrid, Spain. maruxi_@yahoo.es
Rama-Iñiguez
S
S
Sánchez-Brunete
J A
JA
Torrado
J J
JJ
Alunda
J M
JM
Bolás-Fernández
F
F
D000666:Amphotericin B / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000917:Antibody Formation; D018941:Antigens, CD19 / Q000032:analysis; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes; D002455:Cell Division; D002626:Chemistry, Pharmaceutical; D006224:Cricetinae; D005434:Flow Cytometry; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology; D008099:Liver / Q000469:parasitology; D008647:Mesocricetus; D008863:Microspheres; D023421:Models, Animal; D013154:Spleen / Q000276:immunology / Q000469:parasitology
D018941:Antigens, CD19; D000981:Antiprotozoal Agents; D000666:Amphotericin B