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 - http://www.scopus.com/inward/record.url?scp=85074764691&partnerID=8YFLogxK
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 -