Hanne Mørck Nielsen
Lektor
E-mail: hmn(at)farma.ku.dk  
Telefon: 35 33 63 46
Rum: 13/425

Theses in English'

Antimicrobial peptide-loaded catheters
Health care-associated bacterial infections are a growing concern and expense worldwide. Devices such as catheters are subject to bacterial colonisation and subsequent formation of a bacterial biofilm. In patients undergoing long-term catheterisation, recurrent urinary tract infections are therefore common. The treatment of the infection is costly, environmentally detrimental, can lead to development of bacterial resistance, and involves side effects and discomfort for the patient. The overall aim is to develop an advanced material that is resistant to bacterial colonization. The project will explore methods for loading and releasing formulations (e.g. hydrogels) of antimicrobial peptides using a silicone nano-network and will seek to understand and optimize the interplay between material, peptide, and formulation. The project will employ various formulation techniques as well as spectroscopic and microscopic methods.
Supervisor: Eva Horn Møller/Hanne Mørck Nielsen and PhD student associated with the project

Delivery of biopharmaceuticals and particulate drug delivery systems into and across mucosal (oral) epithelium
There is a strong wish to be able to administer e.g. peptide drugs via the oral route. However, these drugs often need to be both protected against degradation and aided with regard to transport of the drug across the mucosal membrane barrier. In the present project, various aspects of mucosal / oral delivery of peptides will be addressed.

Mechanistic studies of the peptides formulated in an optimal formulation; i.e. consisting of the peptide in solution, as complexes, precipitates or nanoparticles will be carried out. The delivery systems will be based on biopolymers such as PLGA and chitosan, or lipids. The delivery system will be characterized and tested with respect to delivery of the active biopharmaceutical. Assessment of the desired enhancer effect will be weighed against unwanted effects, such as cellular toxicity and membrane integrity. The delivery systems may be investigated in biologically relevant in vitro settings, different cell-based in vitro models potentially along with in vivo studies.
Supervisors: Hanne Mørck Nielsen. PhD student associated with the project

Formulation of novel antimicrobial nanomedicine
Bacterial infections are a world-wide problem and the challenges related to efficient treatment of infections include that novel drug candidates, such as antimicrobial peptides, and delivery systems are thoroughly characterized. The efficiency of an antimicrobial drug can be improved by rational design of a suitable delivery system. By improved targeting to the diseased tissue/cells and use of lower amounts of antimicrobial drug, the risk of resistance development is likely to decrease. Antimicrobial peptides and peptidomimetics (AMPs) have promising characteristics as novel antimicrobial drugs.

The present project will focus on development of drug delivery systems intended for preventing or treating microbial infections. A major part of these studies will be aimed at generating a thorough understanding of the mechanisms of interaction with and transport through eukaryotic as well as prokaryotic cell membranes. This will be done by use of bacterial, cell culture models and model systems consisting of vesicle lipid bilayers, supported bilayers, and applying methodologies based on fluorescence, calorimetry, and different types of microscopy.

The project is a part of the Danish Center for Antibiotic Research and Development, and in collaboration with scientists at the Department of Medicinal Chemistry and at Statens Serum Institute.
Supervisors: Hanne Mørck Nielsen. PhD students associated with the project.

Cell penetrating peptides for improved delivery of drugs
Recent studies have shown that some peptides are able to transport large therapeutic macromolecules and particles (delivery systems) across cell membranes. These are known as cell penetrating peptides (CPP). This project deals with the exploitation of the CPPs properties in achieving transmembrane delivery of active biomacromolecules.
The project focuses on mechanistic studies of the interaction between CPP and cell membranes, and may include work with quantitation of the degree of penetration, stability and toxicity as well as more qualitative methods (e.g. confocal microscopy) for the localization of CPP in cells. Bioanalytical methods can be implemented more or less in the project. Well-known CPPs as well as novel peptides and peptide mimetics may be investigated either alone or in particulate delivery systems.
Supervisors: Hanne Mørck Nielsen. PhD student associated with the project.

Peptide interaction with lipid bilayers
Membrane active peptides such as antimicrobial peptides or cell penetrating peptides are known to interact with lipid bilayers of bacterial or human cells. A mechanistic examination of the mechanism of interaction with these bilayers will give insight into important structural properties of the investigated peptide in relation to the surface adsorption. Using specialized techniques such as the total internal reflection fluorescence (TIRF), it is possible to study this interaction in detail.
Supervisors: Hanne Mørck Nielsen / Lene Jørgensen. PhD student associated with the project

 Industrial project: Nanoparticles for drug delivery to the skin
The use of lipid-based nanoparticulate systems and their potential as topical drug delivery systems for treatment of skin diseases is an area of increasing attention. The focus of the present project is the evaluation of the composition of different lipid nanoparticulate systems (i.e. SLN and nanoemulsions) on their physicochemical properties as well as their skin penetration properties. More specifically this will include (I) preparation of lipid nanoparticulate systems with e.g. different levels of surfactants and different particle size, (II) characterization of the physicochemical properties of these systems and (III) biopharmaceutical evaluation of selected particulate drug delivery systems. The experimental methods may involve determination of particle size, zetapotential, drug substance solubility and surface tension measurements. Furthermore, in vitro skin penetration an in vivo skin irritation studies may be carried out to evaluate the correlation between the physicochemical and the biopharmaceutical properties upon application to the skin.
Internal supervisor: Hanne Mørck Nielsen / LEO Supervisors: Karsten Petersson and Louise Bastholm Jensen