PLGA-PEG-COOH nanoparticles are efficient systems for delivery of mefloquine to Echinococcus multilocularis metacestodes

• Published in: Experimental parasitology Vol. 265; p. 108811
• Main Authors: Autier, Brice, Verger, Alexis, Plaisse, Charleen, Manuel, Christelle, Chollet-Krugler, Marylène, Preza, Matias, Lundstroem-Stadelmann, Britta, Amela-Cortes, Marian, Aninat, Caroline, Samson, Michel, Brandhonneur, Nolwenn, Dion, Sarah
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2024; Elsevier
• Subjects: Alveolar echinococcosis; Animals; Anthelmintics - administration & dosage; Anthelmintics - chemistry; Anthelmintics - pharmacology; Drug delivery system; Drug Delivery Systems; Drug therapy; Echinococcosis - drug therapy; Echinococcus multilocularis - drug effects; EmPGI; Female; Humans; Life Sciences; Mefloquine - administration & dosage; Mefloquine - pharmacology; Mice; Mice, Inbred BALB C; Microbiology and Parasitology; Nanoparticles - chemistry; poly(lactic co-glycolic acid); Polyethylene Glycols - chemistry; Polyglactin 910; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Alveolar echinococcosis; Drug therapy; EmPGI; Drug delivery system; poly(lactic co-glycolic acid)
• ISSN: 0014-4894; 1090-2449; 1090-2449
• DOI: 10.1016/j.exppara.2024.108811

Alveolar echinococcosis (AE) is a severe disease caused by the infection with the larval stage of Echinococcus multilocularis, the metacestode. As there is no actual curative drug therapy, recommendations to manage AE patients are based on radical surgery and prophylactic administration of albendazole or mebendazole during 2 years to prevent relapses. There is an urgent need for new therapeutic strategies for the management of AE, as the drugs in use are only parasitostatic, and can induce toxicity. This study aimed at developing a drug delivery system for mefloquine, an antiparasitic compound which is highly active against E. multilocularis in vitro and in experimentally infected mice. We formulated mefloquine-loaded PLGA-PEG-COOH (poly-(lactic-co-glycolic acid)) nanoparticles that exhibit stable physical properties and mefloquine content. These nanoparticles crossed the outer acellular laminated layer of metacestodes in vitro and delivered their content to the inner germinal layer within less than 5 min. The in vitro anti-echinococcal activity of mefloquine was not altered during the formulation process. However, toxicity against hepatocytes was not reduced when compared to free mefloquine. Altogether, this study shows that mefloquine-loaded PLGA-PEG-COOH nanoparticles are promising candidates for drug delivery during AE treatment. However, strategies for direct parasite-specific targeting of these particles should be developed. [Display omitted] •Mefloquine-loaded PLGA-PEG-COOH nanoparticles (NPs) were physically stable.•Mefloquine content of NPs was stable at least 90 days at 4 °C.•PLGA-PEG-COOH NPs reach the germinal layer of E. multilocularis metacestodes.•Parasitocidal activity of 60 μM mefloquine was not altered by formulation process.•A targeting strategy could be needed in order to avoid side effects.