title: Size dependent skin penetration of nanoparticles in murine and porcine dermatitis models.
abstract: A major limitation in the current topical treatment of inflammatory skin diseases is the inability to selectively deliver the drug to the inflammation site. Recently, smart drug delivery systems such as nanocarriers are being investigated to enhance the selective deposition of anti-inflammatory drugs in inflamed areas of the skin to achieve higher therapeutic efficacy with minimal side effects. Of such systems, polymeric nanoparticles are considered very efficient carriers for the topical drug delivery. In the current work, poly(l-lactide-co-glycolide) nanoparticles of nominal sizes of 70nm (NP70) and 300nm (NP300) were studied for their intra-epidermal distribution in murine and pig atopic dermatitis models over time against the respective healthy controls. Confocal laser scanning microscopical examination of skin biopsies was utilized for the qualitative and semi-quantitative analyses of nanoparticles skin deposition and penetration depth. While no skin penetration was found for any of the particles in healthy skin, the accumulation of NP70 was significantly higher than NP300 in inflamed skin (15-fold in mice, 5-fold in pigs). Penetration depth of NP70 decreased over time in mice from 55±3μm to 20±2μm and similar tendencies were observed for the other formulations. In inflamed pig skin, a similar trend was found for the penetration depth (NP70: 46±12μm versus NP300: 23±3μm); however, the NP amount remained constant for the whole analyzed period. Their ability to penetrate specifically into inflamed skin combined with minimal effects on healthy skin underlines small polymeric nanoparticles' potential as selective drug carriers in future treatment of chronic inflammatory skin diseases such as atopic dermatitis.
authors.affiliation: FDE EA4267, University of Bourgogne Franche-Comté, F-25000 Besançon, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Try
authors.affiliation: FDE EA4267, University of Bourgogne Franche-Comté, F-25000 Besançon, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Moulari
authors.affiliation: FDE EA4267, University of Bourgogne Franche-Comté, F-25000 Besançon, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Béduneau
authors.affiliation: Interactions Cellules Environnement UPSP 2011.03.101, Unité Dermatologique, Laboratoire de Dermatopathologie, BetAgro Sup Campus Vétérinaire de Lyon, Marcy l'Etoile F-69280, France.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fantini
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: Didier
authors.initials: D
authors.lastname: Pin
authors.affiliation: FDE EA4267, University of Bourgogne Franche-Comté, F-25000 Besançon, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Pellequer
authors.affiliation: FDE EA4267, University of Bourgogne Franche-Comté, F-25000 Besançon, France; Department of Pharmaceutics, School of Pharmacy, University of Bonn, Bonn, Germany. Electronic address: alf.lamprecht@uni-bonn.de.
authors.forename: Alf
authors.initials: A
authors.lastname: Lamprecht
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D009924:Organ Culture Techniques; D010316:Particle Size; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D013552:Swine
keywords: Atopic dermatitis; Confocal laser scanning microscopy; Inflamed pig skin model; Polymeric nanoparticles