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.

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