title: Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design.
abstract: Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2(2) full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant - soybean lecithin or sorbitan monooleate and type of co-surfactants - polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential -39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g(-1)) - the main response of interest - confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.
authors.affiliation: Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Cristiane Bastos
authors.initials: CB
authors.lastname: de Mattos
authors.affiliation: Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Débora Fretes
authors.initials: DF
authors.lastname: Argenta
authors.affiliation: Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Gabriela de Lima
authors.initials: Gde L
authors.lastname: Melchiades
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Marlon Norberto Sechini
authors.initials: MN
authors.lastname: Cordeiro
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Maiko Luis
authors.initials: ML
authors.lastname: Tonini
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Milene Hoehr
authors.initials: MH
authors.lastname: Moraes
authors.affiliation: Departamento de Ciências Biológicas, Universidade Regional Integrada do Alto Uruguai e das Missões, Erechim, Rio Grande do Sul, Brazil.
authors.forename: Tanara Beatriz
authors.initials: TB
authors.lastname: Weber
authors.affiliation: Departamento de Ciências Biológicas, Universidade Regional Integrada do Alto Uruguai e das Missões, Erechim, Rio Grande do Sul, Brazil.
authors.forename: Silvane Souza
authors.initials: SS
authors.lastname: Roman
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Nunes
authors.affiliation: Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Helder Ferreira
authors.initials: HF
authors.lastname: Teixeira
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Mário
authors.initials: M
authors.lastname: Steindel
authors.affiliation: Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Letícia Scherer
authors.initials: LS
authors.lastname: Koester
mesh_terms: D000279:Administration, Cutaneous; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002599:Chalcone / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D016503:Drug Delivery Systems; D004655:Emulsions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D054709:Lecithins / Q000737:chemistry / Q000494:pharmacology; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000469:parasitology; D012995:Solubility; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology; D014783:Viscosity
chemical_list: D000977:Antiparasitic Agents; D004655:Emulsions; D054709:Lecithins; D011136:Polysorbates; D013501:Surface-Active Agents; D002599:Chalcone
keywords: chalcone; full factorial; leishmaniasis; nanoemulsion; skin permeation