About the LEO Foundation Center for Cutaneous Drug Delivery
The skin is an organ that often requires drug treatment to alleviate acute and chronic skin diseases. Furthermore, it is easily accessible for application of drugs, and thus also a site for administration of drugs aiming for systemic effects. However, the skin remains a formidable barrier and the delivery of drugs into and across the skin barrier is highly dependent on a number of factors in a complex way.
Considering this, the aim of the LEO Foundation Center for Cutaneous Drug Delivery is to contribute to an integrating knowledge on skin as a barrier for drug absorption, on the one hand, and the properties of drugs and excipients in specific drug delivery systems, on the other.
Through this, we aim to establish an internationally competitive research environment for cutaneous drug delivery research within a 10-year period, based on a predominantly physicochemical approach to develop methods for the rational development of novel and improved drug delivery systems for cutaneous and transcutaneous delivery of both small and large molecules. In doing so, investigations of "on-site" properties of the drug delivery system, taking into account effects in both healthy and impaired skin, play a central role.
With the main outset to build on a physicochemical basis, the Center aims to be clearly visible within the field of cutaneous drug delivery, and differentiated from approaches based on a more empirical development of delivery systems and on clinical work. This approach also allows the Center to be a pivotal point for collaborations with other research fields, ultimately coming together to tackle fundamental questions related to the delivery of drugs to and across the skin.
The LEO Foundation Center for Cutaneous Drug Delivery is made possible by a 10-year grant from the LEO Foundation.
Within a 10-year period, the LEO Foundation Center for Cutaneous Drug Delivery should be recognized as an international excellence center, performing state-of-the-art research and creating innovative solutions within cutaneous drug delivery, with a scientific platform built on integrative physicochemical approaches, including pharmaceutics, as well as novel opportunities in nanotechnology, advanced analytical methodologies, and biological models.
The mission of the LEO Foundation Center for Cutaneous Drug Delivery is to advance the field of cutaneous drug delivery through in-depth physichochemical research, embracing novel opportunities in advanced analytical tools, nanoparticular and other delivery systems, and novel biological model systems.
The Center strives to create and disseminate the newest knowledge on medicines for dermal use, thereby contributing to a solid foundation for the development of effective drug solutions to the skin for the benefit of patients.
The Center is furthermore dedicated to being a central contributor to research training of graduate and under-graduate students
The LEO Foundation Center for Cutaneous Drug Delivery is organized around three research pillars, identified as key for enabling its development:
i) novel analytical tools
ii) novel drug delivery systems
iii) novel biological models.
These pillars are combined with selected indication areas, initially focusing on infection/inflammation, to provide necessary depth to the research, including subsequent indication areas (skin cancer, vaccination) when Center growth allows this to be done without losing critical mass.
Another key element of the development of the Center is interfacing of Center activities with related activities within the Department of Pharmacy. In order to secure this, each pillar will be initially led by a senior staff scientist, who will also be PI for the area during the initial years.
Complementing this, we are currently recruiting three tenure-track Assistant Professors, each focusing on one of these research pillars. Within a 3-5 year period, these are expected to grow into PIs (2nd generation PIs) in their respective area.
In parallel, recruitment of PhD students and activities for Center growth by external funding are ongoing, and steps are taken for integration between the research activities in the three pillars, and between Center activities and activities at the Department of Pharmacy overall.
Professor in Biopharmaceuticals, Biophysics and Drug Delivery at the Department of Pharmacy, University of Copenhagen. Professor at, and previous Chairman of, the Department of Pharmacy, Uppsala University. Previously Director of the Institute for Surface Chemistry in Stockholm, Sweden.
Malmsten's research has resulted in >260 papers, as well as several books and patent families. Parallel to his academic research, he is co-founder of several companies, two developing peptide drugs, and one developing image-guided delivery systems.
Awarded, e.g., the Langmuir Lecture Award from the American Chemical Society and the Norblad-Ekstrand Medal. Member of the Royal Swedish Academy of Engineering Science, Fellow of the Royal Chemical Society, guest professor at Charité University in Berlin, and Editor-in-Chief of the Journal of Colloid and Interface Science.
Malmsten's current research interests include microgels, nanomaterials for drug delivery, as well as antimicrobial, anti-inflammatory, and anticancer peptides.
Professor in Pharmaceutical Design and Drug Delivery at the Department of Pharmacy, University of Copenhagen. Before that he was the Chair in Pharmaceutical Sciences at the National School of Pharmacy, University of Otago, New Zealand from 2003 – 2012. TR has published >340 papers in international peer review journals as well as several book chapters and patents. He is a co-author of the book: Fasttrack: Pharmaceutics - Drug Delivery and Targeting (1st Edition: 2009, 2nd Edition: 2012).
TR is also Editor of the Journal of Pharmaceutical Sciences and the European Journal of Pharmaceutics and Biopharmaceutics, as well as Associate Editor of the Journal of Pharmacy and Pharmacology.
Professor in Biopharmaceuticals and Drug Design, and Research Chair of the Section of Biologics at Department of Pharmacy, University of Copenhagen.
HMN's research has resulted in >100 peer-reviewed papers in recognized international journals and >25 book, patent, and other public scientific publications. Editorial Advisory Board member of the Journal of Pharmaceutical Sciences, Danish Medicines Agency Committee member, and listed on AcademiaNet. HMN's research interests include design of advanced drug delivery systems for macromolecular therapeutics, including antimicrobials, and evaluation of the drug delivery potential through mechanistic studies of specific interactions with biological barrier matrices, such as biofilm, mucosa, and skin.
Associate Professor at Department of Pharmacy, University of Copenhagen, and leader of the Pharmaceutical and Physical Chemistry group. JOE's research has resulted in around 100 peer reviewed papers and a number of other contributions.
Further he is a co-founder of two spin-outs from the Department of Pharmacy. He is currently the EU coordinator of the CRYDIS program, a Research and Innovation Staff Exchange (RISE) project within EU's Horizon 2020 program.
Regarding Novel Analytical Tools, developments in relation to large-scale facilities, notably synchrotron- (MAX IV) and neutron-based (ESS) methodologies are likely to form an internationally competitive experimental platform for soft matter research in the Øresund region, also providing opportunities to scientific collaborations in new constellations.
Considering this, as well as the capability of methods such as X-ray scattering/diffraction and neutron scattering/reflection to provide detailed information about structure and dynamics of formulation- and skin-related systems, connecting the research activities to such large-scale facilities represents a considerable opportunity for the Center.
In addition, there are additional technologies which offer novel opportunities in relation to cutaneous drug delivery research, such as confocal microscopies, various imaging modalities, and related techniques, as well as mass spectrometry-based analysis, allowing studies of the delivery systems themselves, but also of tissue penetration and metabolism.
Regarding Novel Drug Delivery Systems, large recent progress in the nanomaterials area have resulted in considerable current interest in such systems, and also provided novel opportunities within both drug delivery and diagnostics.
Both for more "traditional" nanomaterials, such as surfactant and polymer self-assemblies, and for more exploratory materials, such as various inorganic nanoparticles, recent research has illustrated opportunities to trigger both drug release and various biological responses by a range of parameters, including ionic strength, pH, and temperature, but also by reducing conditions/oxidative stress, and even presence of specific metabolites.
In addition, inorganic nanoparticles may be triggered by external fields such as light/NIR and magnetic fields, allowing simultaneous control of drug delivery and monitoring of therapeutic outcome in theranostic approaches. Again, therefore, embracing such developments is key for the success of the center.
With regards to Novel Biological Models, traditional ex vivo models such as pig skin need to be complemented, e.g., with a battery of model systems for detailed mechanistic studies on transport of both active components and drug carriers.
Furthermore, complementary ex vivo models of healthy and impaired skin is needed, ideally disease-specific, as are corresponding in vivo models, e.g., combined with various techniques for imaging of biological responses. For the latter types of substrates, collaborations with suitable dermatology groups will be developed.
K.L. Browning, I. N. Stocker, P. Gutfreund, S. M. Clarke. J. Colloid Interface Sci. 581 (2021) 682–689
Highly Elastic and Water Stable Zein Microfibers as a Potential Drug Delivery System for Wound Healing
Oxidation of Polyunsaturated Lipid Membranes by UV-Activated Titanium Dioxide Nanoparticles: Role of pH and Salinity
S. Rigo, D. Hürlimann, L. Marot, M. Malmsten, W. Meier, and C. Palivan. ACS Appl. Bio Mater. 2020, 3, 1533.
B.C. Borro, R. Nordström and M. Malmsten. Colloids Surf. B 2020, 187, 110835.
Effects of Charge Contrast and Composition on Microgel Formation and Interactions with Bacteria-Mimicking Liposomes.
B.C. Borro, M.S. Toussaint, S. Bucciarelli, and M. Malmsten. Biochim. Biophys. Acta, accepted for publication.
Malekkhaiat-Häffner, L. Nyström, A. Strömstedt, L. Li, M.J.A. van der Plas, and M. Malmsten. Colloid Interface Sci. 2020, 562, 71.
Nordström, K. Browning, E. Parra-Ortiz, L.S.E. Damgaard, S. Malekkhaiat-Häffner, A. Maestor, R. Campbell, J. Cooper, and M. Malmsten. Colloid Interface Sci. 2020, 562, 322.
Interplay between Amphiphilic Peptides and Nanoparticles for Selective Membrane Destabilisation and Antimicrobial Effects. Malekkhaiat-Häffner and M. Malmsten. Curr. Opinion Colloid Interface Sci. 2019, 44, 59.
Structural Insights into the Combination Effect of Antimicrobial Peptides Reveal a Role of Aromatic-Aromatic Interactions in Antibacterial Synergism. Ilyas, D.K. Lee, M. Malmsten, and A. Bhunia. Biol. Chem. 2019, 294, 14615.
Degradable dendritic nanogels as carriers for antimicrobial peptides. R. Nordström, O.C.J. Andrén, S. Singh, M. Malkoch, M. Davoudi, A. Schmidtchen, M. Malmsten. J. Colloid Interface Sci. October 2019, 554, pp. 592-602
Complexation between antimicrobial peptides and polyelectrolytes. B.C.Borro and M. Malmsten. Advances in Colloid and Interface Science, August 2019, 270, pp. 251-260.
Interaction of Laponite with Membrane Components - Consequences for Bacterial Aggregation and Infection Confinement. S. Malekkhaiat Häffner, L. Nyström, K. Browning, H. Mørck Nielsen, A. Strömstedt, M.J.A. van der Plas, A. Schmidtchen, and M. Malmsten. ACS Appl. Mater. Interf. 2019, 11, 15389.
Antimicrobial Peptide Conjugates of Tungsten Disulfide Quantum Dots for Microbial Targeting in Therapy and Diagnostics. S.A. Mohi, A. Ghorai, H. Ilyas, K. Mroue, G. Narayanan, A. Sarkar, S.K. Ray, K. Biswas. A.K. Bera, M. Malmsten, A. Midya, and A. Bhunia. Colloids Surf. B 2019, 176, 360.
Microgels as Carriers of Antimicrobial Peptides - Effects of Peptide PEGylation. R. Nordström, L. Nyström, H. Ilyas, H.S. Atreya, B.C. Borro, A. Bhunia, and M. Malmsten.Colloids Surf. A 2019, 565, 8.
Microfluidics-Based Self-Assembly of Peptide-Loaded Microgels: Effect of 3D-printed Micromixer Design. B.C. Borro, A. Bohr, S. Bucciarelli, J. Boetcker, C. Foged, J. Rantanen, and M. Malmsten. J. Colloid Interface Sci. 2019, 538, 559.
Effect of Oxidation on the Physicochemical Properties of Polyunsaturated Lipid Membranes. E. Parra-Ortiz, K.L. Browning, L.S.E. Damgaard, R. Nordström, S. Micciulla, S. Bucciarelli, and M. Malmsten. J. Colloid Interface Sci. 2019, 538, 404.
Influence of Self-Assembly on the Performance of Antimicrobial Peptides. S. Malekkhaiat Häffner and M. Malmsten. Curr. Opinion Colloid Interface Sci. 2018, 38, 56.
Avidin-Biotin Cross-Linked Microgel Multilayers as Carriers for Antimicrobial Peptides. L. Nyström, N. Al-Rammahi, S. Malekkhaiat-Häffner, A.A. Strömstedt, K. Browning and M. Malmsten. Biomacromolecules 2018, 19, 4691.
Peptide-Loaded Microgels as Antimicrobial and Anti-Inflammatory Surface Coatings. L. Nyström, AA. Strömstedt, A. Schmidtchen, M. Malmsten. Biomacromolecules. 2018, 19, 3456-3466.
Membrane interactions and cell selectivity of amphiphilic anticancer peptides. L.Nyström, M.Malmsten. Current Opinion in Colloid Interface Science. 2018, 38, 1-17.
Influence of pH on the activity of thrombin-derived antimicrobial peptides. D.A. Holdbrook, S.Singh, Y.K. Choong, J.Petrlova, M. Malmsten, P.J Bond, N.K. Verma, A. Schmidtchen, R.Saravanan. Biochim Biophys Acta 2018, 1860, 2374-2384.
Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides. R. Saravanan, DA. Holdbrook, J. Petrlova, S. Singh, NA. Berglund, YK. Choong, S. Kjellstrom, PJ. Bond, M. Malmsten, A. Schmidtchen. Nature Communications. Volume 9, 2762 (2018)
Transforming nanomedicine manufacturing toward Quality by Design and microfluidics S. Colombo, M. Beck-Broichsitter, J.P. Bøtker, M. Malmsten, J. Rantanen, A. Bohr. Advanced DrugDeliveryReviews 128 (2018) 115–131.
Role for Cela1 in Postnatal Lung Remodeling and AAT-deficient Emphysema R. Joshi, A. Heinz, Q. Fan, S. Guo, B. Monia, CEH. Schmelzer, M. Batie, H. Parameshwaran, BM. Varisco. American Journal of Respiratory Cell and Molecular Biology. 2018 Feb 8.
Degradation of Tropoelastin and Skin Elastin by Neprilysin. A.C. Mora Huertas, C.E.H. Schmelzer, C. Luise, W. Sippl, M. Pietzsch, W. Hoehenwarter, and A. Heinz. Biochimie 2018, 146, 73.
Effects of Bilayer Charge on Lipoprotein Lipid Exchange. K.L. Browning, T. Kjellerup Lind, S. Maric, R.D. Barker, M. Cardenas and M. Malmsten. Colloids Surf. B 168 (2018), 117-125.
Human Lipoproteins at Model Cell Membranes: Effect of Lipoprotein Class on Lipid Exchange. K.L. Browning, T.A. Lind, S. Maric, S. Malekkhaiat-Häffner, G. Nordin Fredrikson, E. Bengtsson, M. Malmsten and M. Cardenas. Sci. Reports 2017, 7:7478, 1.
Delivery Systems for Antimicrobial Peptides. R. Nordström and M. Malmsten. Adv. Colloid Interface Sci. 2017, 242, 17.
Membrane Interactions and Antimicrobial Effects of Layered Double Hydroxide Nanoparticles. S. Malekkhaiat Häffner, L. Nyström, R. Nordström, Z.P. Xu, M. Davoudi, A. Schmidtchen, and M. Malmsten. Phys. Chem. Chem. Phys. 2017, 19, 23832.
Membrane Interactions and Antimicrobial Effects of Inorganic Nanoparticles. S. Malekkhaiat-Häffner, and M. Malmsten. Adv. Colloid Interface Sci. 2017, 248, 105.
Confirmational Aspects of High Content Packing of Antimicrobial Peptides in Polymer Microgels. S. Singh, A. Datta, B.C. Borro, M. Davoudi, A. Schmidtchen, A. Bhunia and M. Malmsten. ACS Appl. Mater. 2017, 9, 40094.
Martin Malmsten delivers presentation on "Host defense peptides to combat infections - from mode-of-action to drug delivery" at the 2nd Skin@Bath Network Symposium, Bath, UK2019.12.10
Martin Malmsten delivering a Keynote Lecture at 8th Conference Bubble and Drop in Bulgaria2019.05.14