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

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

doi:10.1016/j.nano.2019.102121

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

Nanomedicine. 2020 Feb:24:102121. doi: 10.1016/j.nano.2019.102121. Epub 2019 Oct 28.

Authors

Douglas O Escrivani¹, Milene Valéria Lopes², Fernanda Poletto³, Stela Regina Ferrarini⁴, Ariane J Sousa-Batista⁵, Patrick G Steel⁶, Sílvia Stanisçuaski Guterres⁷, Adriana Raffin Pohlmann⁸, Bartira Rossi-Bergmann⁹

Affiliations

¹ Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil. Electronic address: [email protected].
² Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil. Electronic address: [email protected].
³ Departamento de Química Orgânica e Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: [email protected].
⁴ Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: [email protected].
⁵ Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil. Electronic address: [email protected].
⁶ Department of Chemistry, Durham University, UK. Electronic address: [email protected].
⁷ Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: [email protected].
⁸ Departamento de Química Orgânica e Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: [email protected].
⁹ Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil. Electronic address: [email protected].

PMID: 31672601
DOI: 10.1016/j.nano.2019.102121

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.

Keywords: Drug delivery; Leishmaniasis; Lipid-core nanocapsules; Nitrochalcone; Skin; Topical treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Topical
Animals
Antiprotozoal Agents* / chemistry
Antiprotozoal Agents* / pharmacology
Capsules
Female
Leishmania / metabolism
Leishmaniasis, Cutaneous / drug therapy*
Leishmaniasis, Cutaneous / metabolism
Leishmaniasis, Cutaneous / pathology
Lipids* / chemistry
Lipids* / pharmacology
Mice
Mice, Inbred BALB C
Nanostructures* / chemistry
Nanostructures* / therapeutic use

Substances

Antiprotozoal Agents
Capsules
Lipids