Venier-Julienne M C, Vouldoukis I, Monjour L, Benoit J P
Laboratoire de Pharmacie Galénique, Faculté de Pharmacie, Angers, France.
J Drug Target. 1995;3(1):23-9. doi: 10.3109/10611869509015929.
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.
利什曼原虫是专性细胞内寄生虫,可引发利什曼病。利什曼病通过昆虫媒介传播给包括人类在内的脊椎动物宿主。该感染可在体外通过前鞭毛体进行复制,前鞭毛体可感染小鼠常驻腹膜细胞。两性霉素B被包裹在聚(D,L-丙交酯-共-乙交酯)纳米颗粒(可生物降解的药物载体)中,以实现细胞内的特异性靶向。通过将巨噬细胞培养物暴露于药物载体来确定药物与感染细胞的相互作用。在将细胞暴露于载药纳米颗粒之前,先确定了聚合物药物载体的毒性作用。在长达4小时的接触时间内,细胞可耐受0.01%的聚合物浓度。测定了处理后寄生虫的活力。将感染的巨噬细胞与载药和未载药的纳米颗粒以及游离药物一起在26℃下孵育(这可使无鞭毛体转化为前鞭毛体),并记录培养基中寄生虫的数量。观察到无药物纳米颗粒具有抗利什曼原虫活性。这种活性可能是由于巨噬细胞激活后释放过氧化氢所致。两性霉素B的包裹并未增强这种效果。有趣的是,海藻糖(冻干纳米颗粒的冷冻保护剂)改变了寄生虫的生长并激活了巨噬细胞。