title: Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein.
abstract: The aim of this study was to optimize topical nanoemulsions containing genistein, by means of a 23 full factorial design based on physicochemical properties and skin retention. The experimental arrangement was constructed using oil type (isopropyl myristate or castor oil), phospholipid type (distearoylphosphatidylcholine [DSPC] or dioleylphosphaditylcholine [DOPC]), and ionic cosurfactant type (oleic acid or oleylamine) as independent variables. The analysis of variance showed effect of third order for particle size, polydispersity index, and skin retention of genistein. Nanoemulsions composed of isopropyl myristate/DOPC/oleylamine showed the smallest diameter and highest genistein amount in porcine ear skin whereas the formulation composed of isopropyl myristate/DSPC/oleylamine exhibited the lowest polydispersity index. Thus, these two formulations were selected for further studies. The formulations presented positive ζ potential values (>25 mV) and genistein content close to 100% (at 1 mg/mL). The incorporation of genistein in nanoemulsions significantly increased the retention of this isoflavone in epidermis and dermis, especially when the formulation composed by isopropyl myristate/DOPC/oleylamine was used. These results were supported by confocal images. Such formulations exhibited antiherpetic activity in vitro against herpes simplex virus 1 (strain KOS) and herpes simplex virus 22 (strain 333). Taken together, the results show that the genistein-loaded nanoemulsions developed in this study are promising options in herpes treatment.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Débora Fretes
authors.initials: DF
authors.lastname: Argenta
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Cristiane Bastos
authors.initials: CB
authors.lastname: de Mattos
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Fabíola Dallarosa
authors.initials: FD
authors.lastname: Misturini
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Leticia Scherer
authors.initials: LS
authors.lastname: Koester
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Valquiria Linck
authors.initials: VL
authors.lastname: Bassani
authors.affiliation: Programa de Pós-graduação em Farmácia da Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Cláudia Maria Oliveira
authors.initials: CM
authors.lastname: Simões
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Helder Ferreira
authors.initials: HF
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D004655:Emulsions / Q000737:chemistry* / Q000494:pharmacology; D019833:Genistein / Q000737:chemistry* / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D010078:Oxazines; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D012107:Research Design; D012867:Skin; D012869:Skin Absorption; D013552:Swine
chemical_list: D000998:Antiviral Agents; D004655:Emulsions; D010078:Oxazines; D010743:Phospholipids; D019833:Genistein; C044808:nile red
keywords: antiherpetic activity; cationic nanoemulsions; phospholipids; skin retention