title: Interactions of hyaluronic Acid with the skin and implications for the dermal delivery of biomacromolecules.
abstract: Hyaluronic acid (HA) hydrogels are interesting delivery systems for topical applications. Besides moisturizing the skin and improving wound healing, HA facilitates topical drug absorption and is highly compatible with labile biomacromolecules. Hence, in this study we investigated the influence of HA hydrogels with different molecular weights (5 kDa, 100 kDa, 1 MDa) on the skin absorption of the model protein bovine serum albumin (BSA) using fluorescence lifetime imaging microscopy (FLIM). To elucidate the interactions of HA with the stratum corneum and the skin absorption of HA itself, we combined FLIM and Fourier-transform infrared (FTIR) spectroscopy. Our results revealed distinct formulation and skin-dependent effects. In barrier deficient (tape-stripped) skin, BSA alone penetrated into dermal layers. When BSA and HA were applied together, however, penetration was restricted to the epidermis. In normal skin, penetration enhancement of BSA into the epidermis was observed when applying low molecular weight HA (5 kDa). Fluorescence resonance energy transfer analysis indicated close interactions between HA and BSA under these conditions. FTIR spectroscopic analysis of HA interactions with stratum corneum constituents showed an α-helix to β-sheet interconversion of keratin in the stratum corneum, increased skin hydration, and intense interactions between 100 kDa HA and the skin lipids resulting in a more disordered arrangement of the latter. In conclusion, HA hydrogels restricted the delivery of biomacromolecules to the stratum corneum and viable epidermis in barrier deficient skin, and therefore seem to be potential topical drug vehicles. In contrast, HA acted as an enhancer for delivery in normal skin, probably mediated by a combination of cotransport, increased skin hydration, and modifications of the stratum corneum properties.
authors: †Department of Pharmaceutical Sciences, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Madeleine
authors: M
authors: Witting
authors: ‡Department of Physics, Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany.
authors: Alexander
authors: A
authors: Boreham
authors: ‡Department of Physics, Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany.
authors: Robert
authors: R
authors: Brodwolf
authors: §Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic.
authors: Kateřina
authors: K
authors: Vávrová
authors: ‡Department of Physics, Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany.
authors: Ulrike
authors: U
authors: Alexiev
authors: †Department of Pharmaceutical Sciences, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Wolfgang
authors: W
authors: Friess
authors: †Department of Pharmaceutical Sciences, Ludwig-Maximilians-Universität, Munich, Germany.|∥Institute for Pharmaceutical Sciences, Freie Universität Berlin, Berlin, Germany.
authors: Sarah
authors: S
authors: Hedtrich
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002417:Cattle; D006820:Hyaluronic Acid / Q000737:chemistry*; D066298:In Vitro Techniques; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine
chemical_list: D012710:Serum Albumin, Bovine; D006820:Hyaluronic Acid
keywords: FLIM; FTIR; epidermal drug delivery; hyaluronic acid; proteins; skin hydration; skin penetration