Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8

Escrivani, Douglas O; Lopes, Milene Valéria; Poletto, Fernanda; Ferrarini, Stela Regina; Sousa-Batista, Ariane J.; Steel, Patrick G.; Guterres, Sílvia Stanisçuaski; Pohlmann, Adriana Raffin; Rossi-Bergmann, Bartira

Abstract

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.

Citation

Escrivani, D. O., Lopes, M. V., Poletto, F., Ferrarini, S. R., Sousa-Batista, A. J., Steel, P. G., Guterres, S. S., Pohlmann, A. R., & Rossi-Bergmann, B. (2020). Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8. Nanomedicine: Nanotechnology, Biology and Medicine, 24, Article 102121. https://doi.org/10.1016/j.nano.2019.102121

• Journal Article Type: Article
• Online Publication Date: Oct 28, 2019
• Publication Date: Feb 28, 2020
• Deposit Date: Nov 26, 2019
• Publicly Available Date: Oct 28, 2020
• Journal: Nanomedicine: Nanotechnology, Biology and Medicine
• Print ISSN: 1549-9634
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Article Number: 102121
• DOI: https://doi.org/10.1016/j.nano.2019.102121
• Public URL: https://durham-repository.worktribe.com/output/1282729