title: Hyaluronan polymeric micelles for topical drug delivery.
abstract: Nanosized materials offer promising strategy for topical drug delivery due to their enhancing effect on drug percutaneous transport across the stratum corneum barrier. In this work, polymeric micelles made from hydrophobized hyaluronic acid (HA) were probed for skin delivery. Compared to non-polymeric micelle solutions containing similar drug amount, in vitro skin penetration analysis indicated 3 times larger deposition of drug in the epidermis and 6 times larger drug deposition in the dermis after 5h of topical treatment in Franz diffusion cells. The drug deposition was further increased with prolonged time of topical treatment. Laser confocal microscopy revealed the accumulation of both, the HA forming the vehicle and the payload, in the epidermis and dermis. Although fluorescent labeling of the HA would suggest co-transport of the HA and the drug, loading FRET pair dyes in the micellar core clearly demonstrated gradual micelle disruption with increasing skin depth. Transcellular penetration was the predominant pathway for the loaded drug. The HA polymeric micelles also demonstrated increased bioactivity of loaded compound in vitro and in vivo. In addition, the loaded micelles were found to be stable in cream formulations and thus they have great potential for topical applications for cosmetic and pharmaceutical purposes.
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Šmejkalová
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Muthný
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic; Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic. Electronic address: kristina.nesporova@contipro.com.
authors.forename: Kristina
authors.initials: K
authors.lastname: Nešporová
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Hermannová
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic; Faculty of Technology, Department of Chemistry, Tomas Bata University in Zlín, Zlín, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Achbergerová
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic.
authors.forename: Gloria
authors.initials: G
authors.lastname: Huerta-Angeles
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic; Department of Biological and Biochemical Sciences, Faculty of Chemical-Technology, University of Pardubice, Pardubice, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Čepa
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Machalová
authors.affiliation: Institute of Microbiology of the CAS, v.v.i., Prague, Czech Republic; Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University Bratislava, BioMed Martin, Slovakia.
authors.forename: Dominika
authors.initials: D
authors.lastname: Luptáková
authors.affiliation: Contipro a.s., Dolní Dobrouč, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Velebný
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D066298:In Vitro Techniques; D008823:Micelles; D008875:Middle Aged; D011108:Polymers; D012869:Skin Absorption; D063465:Skin Cream; D013552:Swine
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D006820:Hyaluronic Acid
keywords: Hyaluronan; Polymeric micelle; Skin penetration