Specialer
Henrik Jensen
Lektor
E-mail: hj(at)farma.ku.dk
Telefon: 35 33 64 84
Rum: 13/519
Drug – biomacromolcule interactions.
Determination of equilibrium constants and association- and dissociation rate constants. The interaction of a drug substance with a receptor or a protein is usually characterized by a binding or equilibrium constant (K). The equilibrium constant is given by the ratio between the association and the dissociation rate constants (ka/kd). The magnitudes of the rate constants may be of importance to the fate of drug substances in the body. For instance, the dissociation rate constant of a drug – albumin complex may be a determining factor for liver uptake and metabolism of a strongly bound drug. The aim of the project is to develop and validate capillary electrophoresis (CE) and surface plasmon resonance (SPR) methods for the determination of equilibrium and rate constants.
Supervisor: Jesper Østergaard & Henrik Jensen.
Pharmaceutical profiling of drug substances using capillary electrophoresis and electrochemical techniques
The chemical structure of a drug substance determines its degree of interaction with pharmaceutical excipients, e.g. cyclodextrins, surfactants and polymers, propensity for ion pair formation, self association, and distribution in two-phase systems. The objective of the project is to develop new micro techniques based on electrochemistry and capillary electrophoresis for the investigation of distribution and complexation phenomena. The methodologies are characterized by being fast and requiring small amounts of sample only. Hence, they may be used in drug discovery/ early drug development potentially offering a more thorough physical chemical characterization at an earlier time point and a better starting point for subsequent drug development.
Supervisor: Jesper Østergaard & Henrik Jensen.
Adsorption of protein drug compounds to oil-water interfaces
An increasing number of drug compounds under development are based on proteins and other biological macromolecules. This type of drug compounds requires different strategies with respect to development, production and analysis as compared to more traditional drug compounds based on smaller molecules. For example, proteins may change their structure irreversible upon adsorption to interfaces (such as those between water and oil) and thereby loose the pharmacological effect. The purpose of this project is to investigate the adsorption of proteins and other macromolecules to oil-water interfaces using a surface sensitive electrochemical method. Adsorption to the oil-water interface can be compared to adsorption onto modified gold surfaces studied by SPR (Surface Plasmon Resonance) techniques. The adsorption measurements will be supported by studies on protein interactions in aqueous solution in order to investigate how potential excipients may influence the adsorption
Supervisor: Jesper Østergaard & Henrik Jensen.
Development of Drug Sensors for Monitoring Drug Compounds
Throughout the development phase as well as on later stages there is a demand for analytical methods facilitating the measurement of drug compounds in different matrices such as blood, plasma, skin or urine. Traditional approaches typically involve separate sampling, sample preparation separation and detection steps. It will be advantageous if the analysis can be performed on-site and not be dependant on advanced laboratory facilities. The objective of the present project is thus to design sensitive and specific drug sensors. By means of such sensors it will ultimately be possible to monitor individual drugs, their metabolism and disposition and thereby secure proper dosing of the drug compound. In this way unwanted side effects can be avoided. The sensors will mainly be based on electrochemical principles, but techniques based on SPR (Surface Plasmon Resonance) will be included where relevant.
Supervisor: Henrik Jensen
Nanomedicine: New challenges in characterization and development!
During the past few years a revolution has taken place in nanotechnology. By now nanotechnology has matured and can be used in the development of new drug therapies. However, significant challenges related to characterization and development remains. In the present project the focus is on the development of new methods to characterize nanoparticulate drug delivery systems. Traditional analytical chemical procedures are not well-suited for characterization and analysis of these new drugs. New micromethods based on capillary electrophoresis, electrochemistry, surface plasmon resonance and UV-Imaging will therefore be developed. It is of paramount importance that the new methods requires very limited amount of sample as the new nanoparticular drug delivery systems are usually only produced in small amounts. The new methods will allow us to address critical parameters such as incorporation efficiency, release, non-covalent interactions, aggregation and adsorption.
Supervisors: Henrik Jensen & Jesper Østergaard (possibly in collaboration with LEO Pharma).
Osteoarthritis is the most common arthritic disorder characterized by irreversible breakdown of the extracellular matrix (ECM) of the articular cartilage. The latter joint tissue is composed of a complex water-filled polymeric network which might constitute a barrier for drug transport to pharmacological targets located within the ECM, i.e. chondrocytes and enzymes secreted by this cell type. Project objective is to investigate the influence of drug molecular size and physicochemical parameters on transport (diffusion) into the cartilage. Also drug affinity to macromolecular structures comprising the cartilage will be investigated in order to obtain an in depth understanding of basic drug properties that might facilitate transport of anti-arthritic drug candidates into the ECM. The experimental work will encompass development of an artificial joint cartilage model for the study of the ability of model drug compounds to enter into this artificial ECM.
Supervisor: Jesper Østergaard, Claus Selch Larsen, Henrik Jensen, Susan Weng Larsen & Anan Yaghmur.
