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: Thomas Schmidts, Kay Marquardt, Peggy Schlupp, Dorota Dobler, Florian Heinz, Ulf Mäder, Holger Garn, Harald Renz, Jana Zeitvogel, Thomas Werfel, Frank Runkel
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 431 Issue 1-2 Pg. 61-9 (Jul 15 2012) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 22531847 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• DNA, Catalytic
• Drug Carriers
• Emulsions

Topics

• Administration, Cutaneous
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Chromatography, High Pressure Liquid
• DNA, Catalytic (administration & dosage)
• Drug Carriers (administration & dosage)
• Emulsions
• In Vitro Techniques
• Skin (metabolism)
• Skin Absorption
• Swine