In vitro study of the anti-leishmanial activity of biodegradable nanoparticles.
Leishmania are obligate intracellular parasites, responsible for leishmaniasis. Leishmaniasis are transmitted via insect vector to vertebrate hosts including humans. The infection was reproduced in vitro with promastigotes which can infect murine resident peritoneal cells. Amphotericin B was incorporated into poly(D, L-lactide-co-glycolide) nanoparticles, biodegradable drug carriers, to allow specific targeting inside the cell. The interaction of the drug with infected cells was determined by exposing macrophage cultures to drug carriers. The toxic effects of polymeric drug carriers were defined prior to exposing cells to drug-loaded nanoparticles. For contact times up to 4h, cells tolerated polymer concentrations of 0.01%. The viability of parasites after treatment was determined. Infected macrophages were incubated at 26 degrees C (which allows the transformation of amastigote to promastigote) along with loaded and unloaded nanoparticles, as well as the free drug alone, and a count of the parasites in the medium was recorded. Anti-leishmanial activity was observed with drug-free nanoparticles. This activity may arise through the release of hydrogen peroxide following the activation of macrophages. The incorporation of amphotericin B did not enhance this effect. Interestingly, trehalose, a cryoprotector of the freeze-dried nanoparticles, altered parasite growth and activated macrophages.
Venier-Julienne
M C
MC
Laboratoire de Pharmacie Galénique, Faculté de Pharmacie, Angers, France.
Vouldoukis
I
I
Monjour
L
L
Benoit
J P
JP
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001672:Biocompatible Materials; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D006861:Hydrogen Peroxide / Q000378:metabolism; D019344:Lactic Acid; D018314:Leishmania infantum; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D014199:Trehalose / Q000494:pharmacology
D000981:Antiprotozoal Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000666:Amphotericin B; D014199:Trehalose; D006861:Hydrogen Peroxide