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In vitro study of the anti-leishmanial activity of biodegradable nanoparticles
M C Venier-Julienne1, I Vouldoukis, L Monjour
1Laboratoire de Pharmacie Galénique, Faculté de Pharmacie, Angers, France.
Abstract:
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.
Insights
Biodegradable nanoparticles showed anti-leishmanial activity against Leishmania parasites. This effect, potentially from macrophage activation, was not enhanced by amphotericin B, but trehalose altered parasite growth.
Area of Science:
- Parasitology
- Nanotechnology
- Pharmacology
Background:
- Leishmania parasites cause leishmaniasis, transmitted by insect vectors.
- Developing effective treatments for leishmaniasis remains a challenge.
- Nanoparticles offer potential for targeted drug delivery against intracellular parasites.
Purpose of the Study:
- To evaluate the anti-leishmanial activity of amphotericin B-loaded nanoparticles.
- To assess the toxicity and efficacy of biodegradable drug carriers.
- To investigate the role of nanoparticle components in parasite control.
Main Methods:
- Leishmania infection was reproduced in vitro in murine peritoneal cells.
- Amphotericin B was encapsulated in poly(D, L-lactide-co-glycolide) nanoparticles.
- Macrophage cultures were exposed to loaded/unloaded nanoparticles and free drug; parasite viability was assessed.
Main Results:
- Polymeric nanoparticles showed toxicity at concentrations above 0.01% for 4h.
- Drug-free nanoparticles exhibited anti-leishmanial activity, possibly via macrophage activation and hydrogen peroxide release.
- Amphotericin B incorporation did not enhance this activity.
- Trehalose, a cryoprotector, altered parasite growth and activated macrophages.
Conclusions:
- Biodegradable nanoparticles possess inherent anti-leishmanial properties independent of amphotericin B.
- Macrophage activation and hydrogen peroxide production are potential mechanisms of action.
- Trehalose has a significant impact on both parasite viability and host cell response.