title: Skin penetration and dermal tolerability of acrylic nanocapsules: Influence of the surface charge and a chitosan gel used as vehicle.
abstract: For an improved understanding of the relevant particle features for cutaneous use, we studied the effect of the surface charge of acrylic nanocapsules (around 150nm) and the effect of a chitosan gel vehicle on the particle penetration into normal and stripped human skin ex vivo as well as local tolerability (cytotoxicity and irritancy). Rhodamin-tagged nanocapsules penetrated and remained in the stratum corneum. Penetration of cationic nanocapsules exceeded the penetration of anionic nanocapsules. When applied on stripped skin, however, the fluorescence was also recorded in the viable epidermis and dermis. Cationic surface charge and embedding the particles into chitosan gel favored access to deeper skin. Keratinocytes took up the nanocapsules rapidly. Cytotoxicity (viability<80%), following exposure for ≥24h, appears to be due to the surfactant polysorbate 80, used for nanocapsuleś stabilization. Uptake by fibroblasts was low and no cytotoxicity was observed. No irritant reactions were detected in the HET-CAM test. In conclusion, the surface charge and chitosan vehicle, as well as the skin barrier integrity, influence the skin penetration of acrylic nanocapsules. Particle localization in the intact stratum corneum of normal skin and good tolerability make the nanocapsules candidates for topical use on the skin, provided that the polymer wall allows the release of the active encapsulated substance.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: R V
authors.initials: RV
authors.lastname: Contri
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: L A
authors.initials: LA
authors.lastname: Fiel
authors.affiliation: Institut für Pharmazie (Pharmakologie und Toxikologie), Freie Universität Berlin, Berlin, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Alnasif
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Pohlmann
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: S S
authors.initials: SS
authors.lastname: Guterres
authors.affiliation: Institut für Pharmazie (Pharmakologie und Toxikologie), Freie Universität Berlin, Berlin, Germany. Electronic address: monika.schaefer-korting@fu-berlin.de.
authors.forename: M
authors.initials: M
authors.lastname: Schäfer-Korting
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005782:Gels / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D053769:Nanocapsules / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects*; D013499:Surface Properties
chemical_list: D005782:Gels; D053769:Nanocapsules; D011109:Polymethacrylic Acids; D011136:Polysorbates; C038300:methylmethacrylate-methacrylic acid copolymer; D048271:Chitosan
keywords: Chitosan; Cytotoxicity; Irritancy; Nanocapsules; Polymer; Skin penetration