title: Development of drug delivery systems for the dermal application of therapeutic DNAzymes.
abstract: DNAzymes are potent novel drugs for the treatment of inflammatory diseases such as atopic dermatitis. DNAzymes represent a novel class of pharmaceuticals that fulfil a causal therapy by interruption of the inflammation cascade at its origin. There are two challenges regarding the dermal application of DNAzymes: the large molecular weight and the sensitivity to DNases as part of the natural skin flora. To overcome these limitations suitable carrier systems have to be considered. Nano-sized drug carrier systems (submicron emulsions, microemulsions) are known to improve the skin uptake of drugs due to their ability to interact with the skin's lipids. To protect the drug against degradation, the hydrophilic drug may be incorporated into the inner aqueous phase of carrier systems, such as water-in-oil-in-water multiple emulsions. In the present study various emulsions of pharmaceutical grade were produced. Their physicochemical properties were determined and the influence of preservation systems on stability was tested. Drug release and skin uptake studies using various skin conditions and experimental set-ups were conducted. Furthermore, cellular uptake was determined by flow cytometric analysis. The investigations revealed that the developed multiple emulsion is a suitable and promising drug carrier system for the topical application of DNAzyme.
authors.affiliation: Institute of Bioprocess Engineering and Pharmaceutical Technology, Technische Hochschule Mittelhessen - University of Applied Science, Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidts
authors.forename: Kay
authors.initials: K
authors.lastname: Marquardt
authors.forename: Peggy
authors.initials: P
authors.lastname: Schlupp
authors.forename: Dorota
authors.initials: D
authors.lastname: Dobler
authors.forename: Florian
authors.initials: F
authors.lastname: Heinz
authors.forename: Ulf
authors.initials: U
authors.lastname: Mäder
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
authors.forename: Jana
authors.initials: J
authors.lastname: Zeitvogel
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
authors.forename: Frank
authors.initials: F
authors.lastname: Runkel
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D021881:DNA, Catalytic / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage*; D004655:Emulsions; D066298:In Vitro Techniques; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; D021881:DNA, Catalytic; D004337:Drug Carriers; D004655:Emulsions