Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8.
Cutaneous leishmaniasis (CL) is a neglected parasitic disease conventionally treated by multiple injections with systemically toxic drugs. Aiming at a more acceptable therapy, we developed lipid-core nanocapsules (LNCs) entrapping the potent antileishmanial chalcone (CH8) for topical application. Rhodamine-labeled LNC (Rho-LNC-CH8) was produced for imaging studies. LNC-CH8 and Rho-LNC-CH8 had narrow size distributions (polydispersity index <0.10), with similar mean sizes (~180 nm) by dynamic light scattering. In vitro, Rho-LNC-CH8 was rapidly internalized by extracellular Leishmania amazonensis parasites macrophages in less than 15 min. LNC-CH8 activated macrophage oxidative mechanisms more efficiently than CH8, and was more selectively toxic against the intracellular parasites. In vivo, topically applied Rho-LNC-CH8 efficiently permeated mouse skin. In L. amazonensis-infected mice, LNC-CH8 reduced the parasite load by 86% after three weeks of daily topical treatment, while free CH8 was ineffective. In conclusion, LNC-CH8 has strong potential as a novel topical formulation for CL treatment.
['Escrivani|Douglas O|DO|', 'Lopes|Milene Valéria|MV|', 'Poletto|Fernanda|F|', 'Ferrarini|Stela Regina|SR|', 'Sousa-Batista|Ariane J|AJ|', 'Steel|Patrick G|PG|', 'Guterres|Sílvia Stanisçuaski|SS|', 'Pohlmann|Adriana Raffin|AR|', 'Rossi-Bergmann|Bartira|B|']
D000287:Administration, Topical D000818:Animals D000981:Antiprotozoal Agents D002214:Capsules D005260:Female D007891:Leishmania D016773:Leishmaniasis, Cutaneous D008055:Lipids D051379:Mice D008807:Mice, Inbred BALB C D049329:Nanostructures
Lipid-core nanocapsules Topical treatment Leishmaniasis Skin Drug delivery Nitrochalcone