Dr. Gary Martin
King's College
University of London

Drug delivery is an essential component in the development of all therapeutic agents. Our current research interests include determining factors affecting the deposition of powders in and absorption of drugs from the lung, developing means of triggering release of drugs to the colon, examining the effects of mucus on drug delivery, and investigating possible methods of achieving intradermal delivery of drugs.

An investigation of the intra-dermal drug delivery properties of polysaccharide containing formualtions

The localised delivery of a reservoir of drugs to the epidermal layer of the skin can be extremely beneficial for the treatment of a number of conditions including osteoarthritic pain, actinic keratosis and psoriasis. Hyaluronan (HA) is a naturally occurring polysaccharide and has a protective, shock-absorbing and structure stabilising role in connective tissue. Its rhealogical properties have lead to its use as a surgical tool in ophthalmology, the supplementation of joint fluid for the treatment of arthritis, a mucoadhesive as a drug delivery vehicle. Recently, work carried out in our laboratories has demonstrated the potential hyaluronan containing formulations in localising drugs, although the precise mechanism of action of hyaluronan has yet to be identified. To date most of our studies have employed anti-inflammatory agent, diclofenac.

There is scope to develop a number of projects in this area ranging from those that are more chemically based, such as those examining the potential interaction between polysaccharides and drugs and the effect of polysaccharides on drug-protein binding, in vitro, through to those that are more biologically based, such as those examining the diffusion of drugs through human skin. Two examples of project areas are outlined below:-

Project 1: The interaction of drugs with polysaccharides

This project will investigate the potential interactions using fluorescence techniques, size exclusion chromatography, ultrafiltration, equilibrium dialysis and possibly circular dichroism (CD). Interactions will be assessed by dye displacement methodology and the nature and affinity of interactions by suitable binding titrations. The influence of various parameters such as hydration, pH and ionic strength on any identified interactions will be examined. Other techniques will be used to provide confirmatory data.

Project 2: The delivery of drugs to the skin using hyaluronan

The aim of this project will be to identify the mechanism of action of hyaluronan in targeting drugs to the skin. partition coefficients between drug formulations containing various polysaccharides and skin will be determined and compared to those obtained in the absence of polysaccharide. The diffusion of drugs into the human skin will be examined and the influence of formulation excipients on drug deposition determined. The project will involve the use of radiotracer techniques and high performance liquid chromatography to assay the drug.

Both of these projects will enable the potential of endogenous polysaccharides to target drugs to the epidermis. Such targeting will lead to the development of drug formulations with fewer side-effects and greater efficiency of delivery.

As part of the training program provided students will be encouraged to attend in-house postgraduate seminars, in which research students undertaking work in a variety of different disciplines describe the progress of their studies. An opportunity will be provided to visit our collaborators’ laboratories at the St. Bartholomew’s Medical School.