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

TY - JOUR

T1 - Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8

AU - O. Escrivani, Douglas

AU - Lopes, Milene Valéria

AU - Poletto, Fernanda

AU - Ferrarini, Stela Regina

AU - Sousa-Batista, Ariane J.

AU - Steel, Patrick G.

AU - Guterres, Sílvia Stanisçuaski

AU - Pohlmann, Adriana Raffin

AU - Rossi-Bergmann, Bartira

N1 - Funding Information: Funding source: We thank the Brazilian agencies CAPES, CNPq, and FAPERGS for financial support of this project and The Royal Society London for an International Collaboration Award for Research Professors (#IC160044 to BRB and PGS). Publisher Copyright: © 2019 Elsevier Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - Drug delivery

KW - Leishmaniasis

KW - Lipid-core nanocapsules

KW - Nitrochalcone

KW - Skin

KW - Topical treatment

UR - https://www.scopus.com/pages/publications/85074764691

U2 - 10.1016/j.nano.2019.102121

DO - 10.1016/j.nano.2019.102121

M3 - Article

C2 - 31672601

AN - SCOPUS:85074764691

SN - 1549-9634

VL - 24

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

M1 - 102121

ER -