Dermal Drug Delivery

Our mission


We strive to improve drug delivery for different therapeutic targets via the dermal route and to elucidate the mechanisms behind changes in skin physiology that result in altered barrier function. Through innovative formulation design we aim to find optimised solutions for new therapeutic entities or cosmetic agents that we test in pre-clinical and clinical settings.

Our work


Skin physiology is a complex matter with great intra- and inter-individual variability. Through our work, we aim to elucidate correlations between molecular properties of skin and its function as main barrier against the environment. Methodologically, we combine classic in vitro and ex vivo techniques for pre-clinical evaluation as well as in vivo studies on human volunteers for evaluation of formulations and individual compounds. Thus, we strive to acquire detailed understanding of the factors governing skin penetration of drugs. Understanding the relationships between drug, vehicle and skin is a prerequisite for the design of new drug delivery systems and ultimate therapeutic success.

Research Topics


  • Lipid-Based Colloidal Drug Carrier Systems

Optimized dermal drug delivery systems are developed, characterized and tested for their effect on skin physiology and barrier function. Among those, we focus on drug carriers based on sustainable compounds, such as lecithin- or sugar-based surfactants. Colloidal carriers include nanoemulsions, liposomes, lyotropic liquid crystalline phases a.k.a. microemulsions, lipid nanoparticles and nanostructured lipid carriers.

  • Skin Physiology

Skin compatibility of developed formulations and individual compounds is of major importance in dermal drug delivery and cosmetic applications. We combine classic non-invasive biophysical techniques as well as latest spectroscopic tools for analysis of physiological skin parameters. Analyzed skin properties include transepidermal water loss, skin hydration, skin surface lipids and pH, skin microrelief, pigmentation and erythema. Individual skin status can be characterized non-invasively in regard to natural moisturizing factor, urea content, skin lipid profile and stratum corneum proteins.

  • Penetration Enhancement Strategies and Penetration Models

The effect of classic penetration enhancers is well-known, though underlying mechanisms are not always clear. We strive to elucidate ways to promote the penetration of drugs into the skin while keeping an eye on real-life aspects that may ultimately affect drug delivery. Though established models exist, we aim to follow a holistic strategy including environmental factors. The design of alternative penetration models is ongoing.

  • Effect of Sunlight on Skin Physiology

Exposure to sunlight is associated with both benefits and risks to our organism. We are interested in the effects of sunlight on skin in regard to skin physiology, skin ageing and cancer development. Apart from the design of protective sunscreens and their analysis, our research focusses on the analysis of drug-induced phototoxic effects.

Methods


Classic permeation/penetration methods and vibrational spectroscopy: Among the classic techniques for permeation/penetration analysis we use static Franz-type diffusion cells with different model membranes (porcine, human, synthetic) as well as tape stripping on the porcine ear model or human forearm skin in vivo. Advanced spectroscopic approaches for skin penetration analysis include ATR-FTIR spectroscopy ex vivo and confocal Raman spectroscopy ex vivo and in vivo.   

Cell culture models: In vitro methods to analyse the skin compatibility of formulations, drugs and additives involve 2D cell culture models using human primary cells from healthy donors. Human keratinocytes and fibroblasts are used, standard essays include cytotoxicity assays (MTT, BrdU) and scratch assays to investigate wound healing.

Characterization of formulations: Formulation analysis involves a range of established tools including light scattering-based techniques for analysis of particle size and zeta potential, flow and oscillatory rheometry and microcalorimetry.

Analysis of skin physiology: Biophysical techniques for skin analysis include a closed condenser-chamber probe for measurement of the transepidermal water loss (Aquaflux®), a corneometer®, skin pH-Meter® and Sebumeter® as well as a capacitance-based skin surface sensor (Epsilon®) and confocal Raman spectrometer (Skin Composition Analyzer gen2-SCA).

 

 

Cooperative strategies


We follow up on different fruitful co-operations with research partners both nationally and internationally. Cell culture research and clinical studies are done in cooperation with our partners at the Medical University of Vienna. Spectrosopic analyses are performed in cooperation with our partners at the Faculty of Chemistry, University of Vienna, and the Eberhard Karls University Tübingen, Germany. Morphological analyses of colloidal drug delivery systems are done in cooperation with the Vienna Biocenter Core Facilities. 

Funding


  • 2012 - 2020 Research Platform   Characterization of Drug Delivery Systems on Skin and Involved Mechanisms
  • 2018 - 2020 Project   Development and analysis of different phospholipid formulations for dermal application and their effect on human dermal cell viability, Phospholipid Research Center Heidelberg, Projekt CVA-2018-063/2-1, www.phospholipid-research-center.com
  • 2015 - 2019 Project   Development of Topical Formulations, CIS GmbH Vienna  
  • 2014 - 2017 Project   Development of NLC and nanoemulsions with monoacyl-phospholipids and influence on the skin barrier in vitro and in vivo, Phospholipid Research Center Heidelberg, Projekt CVA-2015-035/1-1,
    www.phospholipid-research-center.com
  •  2012 - 2017 Project   Simultaneous Determination of Skin Penetration of Drug and Vehicle Compounds,
    FWF P 24846-B20
  • 2011 – 2019 Project   Chemical and Physical Stability of Magistral Formulations, Bayer Austria

 

 

Publications


• Original Articles

C. Vater, V. Hlawaty, P. Werdenits, M.A. Cichon, V. Klang*, A. Elbe-Bürger, M. Wirth, C. Valenta, Effects of lecithin-based nanoemulsions on skin: short-time cytotoxicity MTT and BrdU studies, skin penetration of surfactants and additives and the delivery of curcumin, Int. J. Pharm. 580 (2020) 119209,  doi: 10.1016/j.ijpharm.2020.11920

A. Pany, M. Wohlgenannt, S. Klopprogge, M. Wolzt, T. Heuser, H. Kotisch, C. Valenta, V. Klang*, Effect of hydroxypropyl-β-cyclodextrin in fluid and semi-solid submicron emulsions on physiological skin parameters during regular in vivo application. Int. J. Cosm. Sci. (2021), 1-6. doi: 10.1111/ics.12674.

L. Binder, V. Klang*, S. Sheikh Rezaei, O. Neuer, Z. Zhang, D.J. Lunter, M. Wolzt, C. Valenta, Topical application of highly concentrated water-in-oil emulsions: Physiological skin parameters and skin penetration in vivo - A pilot study. Int. J. Pharm. 571 (2019) 118694, doi: 10.1016/j.ijpharm.2019.118694.

C. Vater, A. Adamovic, L. Ruttensteiner, K. Steiner, P. Tajpara, V. Klang*, A. Elbe-Buerger, M. Wirth, C. Valenta, Cytotoxicity of lecithin-based nanoemulsions on human skin cells and ex vivo skin permeation: comparison to conventional surfactant types. Int. J. Pharm. 566 (2019) 383-390, doi: 10.1016/j.ijpharm.2019.05.078.

A. Pany, V. Klang*, C. Peinhopf, A. Zecevic, J. Ruthofer, C. Valenta, Hair removal and bioavailability of chemicals: Effect of physicochemical properties of drugs and surfactants on skin permeation ex vivo, Int. J. Pharm. 567 (2019) 118477, doi: 10.1016/j.ijpharm.2019.118477.

L. Binder, J. Mazál, R. Petz, V. Klang*, C. Valenta, The role of viscosity on skin penetration from cellulose ether-based hydrogels, Skin Res. Technol. (2019) 00:1-10, doi: 10.1111/srt.12709.

A. Pany, V. Klang*, M. Brunner, J. Ruthofer, E. Schwarz, C. Valenta, Effect of Physical and Chemical Hair Removal Methods on Skin Barrier Function in Vitro: Consequences for a Hydrophilic Model Permeant, Skin Pharmacol. Physiol. 32 (2019) 8-21.

M. Wolf, V. Klang*, T. Stojcic, C. Fuchs, M. Wolzt, C. Valenta*, NLC versus nanoemulsions: effect on physiological skin parameters during regular in vivo application and impact on drug penetration, Int. J. Pharm. 549 (2018) 343-351.

L. Binder, E. M. Kulovits, R. Petz, J. Ruthofer, D. Baurecht, V. Klang*, C. Valenta, Penetration monitoring of drugs and additives by ATR-FTIR spectroscopy/tape stripping and confocal Raman spectroscopy – a comparative study, Eur. J. Pharm. Biopharm. 130 (2018) 214-223.

M. Wolf, F. Reiter, T. Heuser, H. Kotisch, V. Klang, C. Valenta*, Monoacyl-Phospatidylcholine based Drug Delivery Systems for Lipophilic Drugs: Nanostructured Lipid Carriers vs. Nano-sized Emulsions, J. Drug Delivery Sci. Technol. 46 (2018) 490-497.

M. Wolf,  V. Klang*, M. Halper, C. Stix, T. Heuser, H. Kotisch, C. Valenta*, Monoacyl-phospatidylcholine nanostructured lipid carriers: Influence of lipid and surfactant content on in vitro skin permeation of flufenamic acid and fluconazole, J. Drug Delivery Sci. Technol. 41C (2017) 419-430.

C. Nagelreiter, S. Raffeiner, C. Geyerhofer, V. Klang, C. Valenta*, Influence of drug content, type of semi-solid vehicle and rheological properties on the skin penetration of the model drug fludrocortisone acetate. Int. J. Pharm. 448 (2013) 305-312.

V. Klang, C. Valenta, N.B. Matsko*, Analytical Electron Microscopy for Characterization of Fluid or Semi-Solid Multiphase Systems Containing Nanoparticulate Material, Pharmaceutics 5 (2013) 115-126.

V. Klang, A. Novak, M. Wirth, C. Valenta*, Semi-solid O/W emulsions based on sucrose stearates: influence of oil and surfactant type on morphology and rheological properties, J. Disp. Sci. Technol. 34 (2013) 322-333.

V. Klang, J.C. Schwarz, S. Haberfeld, P. Xiao, M. Wirth, C. Valenta*, Skin integrity testing and monitoring of in vitro tape stripping by capacitance-based sensor imaging, Skin Res. Techn. 19 (2013) e259-272.

J.C. Schwarz, V. Klang, M. Hoppel, D. Mahrhauser, C. Valenta*, Natural microemulsions: formulation design and skin interaction, Eur. J. Pharm. Biopharm. 81 (2012) 557-562.

V. Klang, S. Haberfeld, A. Hartl, C. Valenta*, Effect of γ-cyclodextrin on the in vitro skin permeation of a steroidal drug from nanoemulsions: Impact of experimental setup, Int. J. Pharm. 423 (2012) 535-542.

V. Klang and J. Schwarz, B. Lenobel, M. Nadj, J. Auböck, M. Wolzt, C. Valenta*, In Vitro vs in Vivo Tape Stripping: Validation of the Porcine Ear Model and Penetration Assessment of Novel Sucrose Stearate Emulsions, Eur. J. Pharm. Biopharm. 80 (2012) 604-614. Shared first authorship.

J.C. Schwarz and V. Klang, M. Hoppel, M. Wolzt, C. Valenta*, Corneocyte quantification by NIR densitometry and UV/Vis spectroscopy for human and porcine skin and the role of skin cleaning procedures, Skin Pharmacol. Physiol. 25 (2012) 142-149. Shared first authorship.

J.C. Schwarz, V. Klang, S. Karall, D. Mahrhauser, G.P. Resch, C. Valenta*, Optimisation of multiple W/O/W nanoemulsions for dermal delivery of acyclovir, Int. J. Pharm. 435 (2012) 69-75.

V. Klang, J.C. Schwarz, N. Matsko, E. Rezvani, N. El-Hagin, M. Wirth, C. Valenta*, Semi-solid Sucrose Stearate-Based Emulsions as Dermal Drug Delivery Systems, Pharmaceutics 3 (2011) 275-306.

V. Klang, J.C. Schwarz, A. Hartl, C. Valenta*, Facilitating in vitro tape stripping: application of infrared densitometry for quantification of porcine stratum corneum proteins, https://www.karger.com/Article/Abstract/326072Skin Pharmacol. Physiol. 24 (2011) 256-268.

V. Klang, N. Matsko, K. Raupach, N. El-Hagin, C. Valenta*, Development of sucrose stearate-based nanoemulsions and optimisation through γ-cyclodextrin, Eur. J. Pharm. Biopharm. 79 (2011) 58-67.

V. Klang, N. Matsko, A.-M. Zimmermann, E. Vojnikovic, C. Valenta*, Enhancement of stability and skin permeation by sucrose stearate and cyclodextrins in progesterone nanoemulsions, Int. J. Pharm. 393 (2010) 152-160.

S. Hoeller, V. Klang, C. Valenta*, Skin-compatible lecithin drug delivery systems for fluconazole: effect of phosphatidylethanolamine and oleic acid on skin permeation, J. Pharm. Pharmacol. 60 (2008) 587-591.


­• Review Articles and Book Chapters

C. Vater, C. Valenta, V. Klang*, Effects of phospholipids on skin: use of primary human keratinocytes and fibroblasts as 2D cell culture models, in: Percutaneous Absorption: Drugs, Cosmetics, Mechanisms, Methods, 5th edition, Eds.: N. Dragicevic, H.I. Maibach, CRC press, in press

V. Klang, M. Hoppel, C. Valenta*. Infrared Densitometry for In Vitro Tape Stripping: Quantification of Porcine Corneocytes, in: Measuring the skin, 2nd edition, vol. 1, pp. 281-288, Eds. Humbert P, Maibach H, Fanian F, Agache P, Springer Switzerland (2017)

J.C. Kovi-Schwarz, V. Klang, C. Valenta*, ATR-FTIR Spectroscopy and the Skin Barrier: Evaluation of Penetration Enhancement Effects, in: Percutaneous Penetration Enhancers - Drug Penetration Into/Through the Skin: Methodology and General Considerations, N. Dragicevic, H.I. Maibach, Springer-Verlag Berlin Heidelberg, pp. 247-255 (2017)

V. Klang, J.C. Schwarz, C. Valenta*, Nanoemulsions in Dermal Drug Delivery, in: Percutaneous Penetration Enhancers - Chemical Methods in Penetration Enhancement: Drug Manipulation Strategies and Vehicle Effects, Eds. N. Dragicevic, H.I. Maibach, Springer-Verlag Berlin Heidelberg, pp. 255-266 (2015)

V. Klang, N.B. Matsko*. Electron Microscopy of Pharmaceutical Systems, in: Advances in Imaging and Electron Physics, 1st Edition, pp. 125-208 (2014)

V. Klang*, C. Valenta, N.B. Matsko, Electron microscopy of pharmaceutical systems, Micron 44 (2013) 45-74.

V. Klang*, N.B. Matsko*, C. Valenta, F. Hofer, Electron microscopy of nanoemulsions: An essential tool for characterisation and stability assessment, Micron 43 (2012), 85-103.

V. Klang, C. Valenta*, Lecithin-based nanoemulsions, J. Drug Delivery Sci. Technol. 21 (2011), 55-76.