Drug Delivery and Biophysics of Biopharmaceuticals (DDBB)

The DDBB group is based at the Dept. of Pharmacy (University of Copenhagen) and relates to the delivery and (in)stability of peptide and proteins used as drugs (biopharmaceuticals), but also to the use of peptides/proteins as biomaterials. Our research can roughly be divided into two main areas:

Vito Foderà focuses on the understanding of the interaction between peptides/proteins and their surroundings, resulting in their self-assembly into ordered structures. This self-assembly is not only relevant to amyloid diseases like Alzheimer’s and Parkinson’s, but can also be used to prepare biomaterials and novel drug delivery systems. Vito is the PI of the initiative “ProSmart” aimed at investigated protein superstructures as smart biomaterials and funded by a Villum Young Investigator Award. Vito´s work mainly relies on the combination of theoretical modelling using concepts from colloids science and experiments based on spectroscopic methods, X-ray/neutron scattering and microscopy approaches

Hanne Mørck Nielsen’s main research focus is on understanding the mechanisms by which drug delivery of peptides/proteins and antimicrobials is influenced by the various biological barriers to efficient therapy. A variety of nanoscale and microscale delivery systems are designed through assembly of biopolymers, peptides, and lipids, characterized and evaluated to eventually increase the therapeutic potential of biopharmaceutical drugs. The impact with interfaces such as membranes, cells, and epithelia, is studied in detail and exploited for drug delivery purposes. Hanne heads the Center for Biopharmaceuticals and Biobarriers in Drug Delivery.

The Pharmaceutical Physical and Analytical Chemistry

As compared to liposomes, the research area on the pharmaceutical uses of inverse non-lamellar liquid crystalline phases and their corresponding nano-self-assemblies (e.g. cubosomes, hexosomes, and micellar cubosomes) is still in its infancy, but is expected to rapidly grow in the coming years. Recent studies from our laboratory showed that cubosome and hexosome nanoparticles hold promise in the field of drug delivery and sustained drug release, but further optimization is still required before such nanocarriers can truly realize their therapeutic potential in many diseases. In this front, we recently described a simple strategy in engineering of safe lyotropic non-lamellar liquid crystalline aqueous nanodispersions with tunable internal nanostructures that overcomes hemolysis and complement activation in the human blood. Accordingly, such developments can help with realizing the potential of cubosome and hexosome nanodispersions for exploitation in parenteral delivery of drugs and contrast agents. The application of cubosomes and hexosomes for parenteral drug delivery is an ambitious one; however, these nanocarriers may find accelerated applications for oral, ocular and topical delivery of poorly water-soluble drugs, thereby offering an alternative, yet, a cost-effective opportunity in formulation science.

The optimal utilization of these nanodispersions for drug (and functional food) delivery applications requires studying the impact of loading drugs on their internal nanostructures, and fully comprehending the interaction of these drug-loaded dispersed particles with the biological environment to ensure the efficient transportation of the solubilized drugs. In addition, it is of our interest to address the challenges of enhancing the stability of the dispersed nanoparticles under different conditions, and of modulating their nanostructure in order to optimize their loading of different drugs. Improved understanding of multifaceted physicochemical and biological processes modulating the internal nanostructure and stability of these non-lamellar liquid crystalline nanodispersions could lead to development of improved clinical formulations with pharmaceutical attributes.

The Surface and Colloid Chemistry Group, as well as the LEO Foundation Center for Cutaneous Drug Delivery,

Both groups lead by Martin Malmsten and based at the Department of Pharmacy at the University of Copenhagen, are interested in a range of topics related to surface and colloid chemistry aspects of drug delivery, including amphiphilic host defense peptides (AMP), microgels, inorganic nanoparticles for peptide delivery, as well as lipid barriers in cutaneous drug delivery. In our research into these areas, we employ a range of surface and colloid chemistry techniques, such as ellipsometry, QCM-d, ATR-IR, CD, light scattering, and small-angle X-ray scattering. In addition, neutron scattering, mainly neutron reflection but also SANS, are central in our research, e.g., for studies of the interactions of nanoparticulate delivery systems with model cell membranes, and on effects of lipid peroxidation on membrane structure and stability.

1. Microgels as carriers of antimicrobial peptides (PI: Martin Malmsten)

2. Membrane interactions of nanoclays as delivery systems for antimicrobial peptides (PI: Martin Malmsten)

3. Membrane Photooxidation by TiO₂ Nanoparticles – Relation to Antimicrobial Properties (PI: Martin Malmsten)

4. Membrane Interactions of Virus-Like Mesoporous Silica Nanoparticles (PI: Martin Malmsten)

5. Lipid organization in the stratum corneum and consequences for skin drug delivery (PI: Kathryn Browning)

6. BRAIN-PENetrating cubosomal and hexosomal NANOcarriers for glioma-targeting delivery (PI: Anan Yaghmur)

7. Formation and characterization of soft self-assembled drug nanocarriers (PI: Anan Yaghmur)

8. In situ formation of parenteral drug dosage forms with tunable liquid crystalline nanostructures at the site of administration (PI: Anan Yaghmur & Susan Weng Larsen)

9. Development of safer nanomedicines based on cubosomes and hexosomes for parenteral drug delivery applications (PI: Anan Yaghmur) 

10. Development of cancer nanomedicines based on cubosomes and hexosomes (PI: Anan Yaghmur) 

11. Development of nano-self-assemblies based on omega-3 monoglycerides for the co-delivery of nutraceuticals and therapeutic agents (PI: Anan Yaghmur)

12. pH-Switchable Antimicrobial Nano-Self-Assemblies (PI: Stefan Salentinig (University of Fribourg, Switzerland))

13. Epithelial membrane dynamics in drug delivery (PI: Hanne Mørck Nielsen)

14. Peptide- and biopolymer-based assembling drug delivery systems and their delivery potential (PI: Hanne Mørck Nielsen)

15. Membrane-interacting peptides (PI: Hanne Mørck Nielsen)

16. Nanogels for antimicrobial therapy (PI: Sylvia Klodzinska)

17. Nanoparticles improved delivery of antibiotics to biofilms (PI: Feng Wan)

18. Biomaterials for Drug Delivery (PI: Vito Foderà)

19. Biophysics of Protein-Membrane Interaction (PI: Vito Foderà)

20. Protein and Peptide Self-Assembly (PI: Vito Foderà)

21. Protein Particles in Drug Formulations (PI: Vito Foderà)

• Microfluidics-Based Self-Assembly of Peptide-Loaded Microgels: Effect of 3D-printed Micromixer Design,

• Peptide-Loaded Microgels as Antimicrobial and Anti-Inflammatory Surface Coatings,

• Effect of Oxidation on the Physicochemical Properties of Polyunsaturated Lipid Membranes,

• Interaction of Laponite with Membrane Components - Consequences for Bacterial Aggregation and Infection Confinement,

• Direct observation of alpha-lactalbumin, adsorption and incorporation into lipid membrane and formation of lipid/protein hybrid structures. 

• Early Stage Alpha-Synuclein Amyloid Fibrils are Reservoirs of Membrane-Binding Species. 

• Flexibility defines structure in crystals of amphiphilic DNA nanostars. 

• Amphiphilic-DNA Platform for the Design of Crystalline Frameworks with Programmable Structure and Functionality. 

• Ethanol Controls the Self-Assembly and Mesoscopic Properties of Human Insulin Amyloid Spherulites. 

• Interaction with Prefibrillar Species and Amyloid-Like Fibrils Changes the Stiffness of Lipid Bilayers. 

• Trifluoroethanol Modulates α-Synuclein Amyloid-like Aggregate Formation, Stability and Dissolution. 

• Hyaluronic acid-based nanogels improve in vivo compatibility of the anti-biofilm peptide DJK-5. 

• Qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant by using quartz crystal microbalance with dissipation monitoring. 

• Fluorophore labeling of a cell-penetrating peptide significantly alters the mode and degree of biomembrane interaction. 

• Lipid shell-enveloped polymeric nanoparticles with high integrity of lipid shells improve mucus penetration and interaction with cystic fibrosis-related bacterial biofilms. 

• Stereochemistry as a determining factor for the effect of a cell-penetrating peptide on cellular viability and epithelial integrity. 

• Phosphatidylcholine-citrem nano-self-assemblies: Solubilization of bupivacaine and its role in triggering colloidal transition from vesicles to cubosomes and hexosomes. 

• A Hydrodynamic flow focusing microfluidic device for the continuous production of hexosomes based on docosahexaenoic acid monoglyceride. 

• From Structure to Function: pH-Switchable Antimicrobial Nano-Self-Assemblies. 

• Cisplatin encapsulation generates morphologically different multi-compartments in the internal nanostructures of non-lamellar liquid crystalline self-assemblies.

  Azmi, I. D., Østergaard, J., Sturup, S., Gammelgaard, B., Urtti, A., Moghimi, S. M., Yaghmur, A. (2018)  Langmuir, 34, 6570-6581.

• Entrepreneurship in Pharmaceuticals:

• Pharmacy I:

• Pharmacy II:

• Research Project in Pharmaceutics and Drug Delivery:

• Biopharmaceutical Aspects of Drug Delivery:

• Biopharmaceuticals Drug Development

• Pharmaceutical Physical Chemistry 1.

• Pharmaceutical Physical Chemistry 2:

• Biopharmaceuticals: Formulation of Peptides and Proteins

• PhD course Analytical Methodology in Protein Formulation Development 

• Physical Chemistry: 

• Physical Chemistry: 

• Characterization of Drug Substances and Drug Delivery Systems: Lectures on Soft Self-Assembled Drug Delivery Systems