title: Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of resveratrol and curcumin.
abstract: Polyphenols, which are secondary plant metabolites, gain increasing research interest due to their therapeutic potential. Among them, resveratrol and curcumin are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as anticarcinogenic effects. In addition to their individual therapeutic effect, increased activity was reported upon co-delivery of the two compounds. However, due to the poor water solubility of resveratrol and curcumin, their clinical application is currently limited. In this context, lipid-core nanocapsules (LNC) composed of an oily core surrounded by a polymeric shell were introduced as drug carrier systems with the potential to overcome this obstacle. Furthermore, the encapsulation of polyphenols into LNC can increase their photostability. As the attributes of the polyphenols make them excellent candidates for skin treatment, the aim of this study was to investigate the effect of co-delivery of resveratrol and curcumin by LNC upon topical application on excised human skin. In contrast to the formulation with one polyphenol, resveratrol penetrated into deeper skin layers when the co-formulation was applied. Based on vibrational spectroscopy analysis, these effects are most likely due to interactions of curcumin and the stratum corneum, facilitating the skin absorption of the co-administered resveratrol. Furthermore, the interaction of LNC with primary human skin cells was analyzed encountering a cellular uptake within 24h potentially leading to intracellular effects of the polyphenols. Thus, the simultaneous delivery of resveratrol and curcumin by LNC provides an intelligent way for immediate and sustained polyphenol delivery for skin disease treatment.
authors.affiliation: Saarland University, Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), 90610-000 Porto Alegre, RS, Brazil.
authors.forename: Rossana B
authors.initials: RB
authors.lastname: Friedrich
authors.affiliation: Saarland University, Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany; University of Twente, Optical Sciences Group, MESA+ Institute for Nanotechnology, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Birthe
authors.initials: B
authors.lastname: Kann
authors.affiliation: Saarland University, Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), 90610-000 Porto Alegre, RS, Brazil.
authors.forename: Karine
authors.initials: K
authors.lastname: Coradini
authors.affiliation: University of Twente, Optical Sciences Group, MESA+ Institute for Nanotechnology, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Herman L
authors.initials: HL
authors.lastname: Offerhaus
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), 90610-000 Porto Alegre, RS, Brazil.
authors.forename: Ruy C R
authors.initials: RC
authors.lastname: Beck
authors.affiliation: Saarland University, Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany; Helmholtz Centre for Infection Research and Helmholtz Institute for Pharmaceutical Research Saarland, Department of Drug Delivery, Campus A4.1, 66123 Saarbruecken, Germany. Electronic address: m.windbergs@mx.uni-saarland.de.
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D005347:Fibroblasts / Q000187:drug effects; D056604:Grape Seed Extract / Q000008:administration & dosage / Q000737:chemistry; D006601:Hexoses / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D009821:Oils / Q000008:administration & dosage / Q000737:chemistry; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D059808:Polyphenols / Q000008:administration & dosage / Q000737:chemistry; D000077185:Resveratrol; D012869:Skin Absorption; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D056604:Grape Seed Extract; D006601:Hexoses; D053769:Nanocapsules; D009821:Oils; D011091:Polyesters; D059808:Polyphenols; D013267:Stilbenes; C016240:polycaprolactone; D003474:Curcumin; C009298:sorbitan monostearate; D000077185:Resveratrol
keywords: Cellular uptake; Co-encapsulation; Curcumin; Lipid-core nanocapsules; Resveratrol; Skin penetration