Dr. Gary Martin
King's College
University of London
webpageA range of opportunities exist for students to join current ongoing research within the fields of drug synthesis and drug delivery in particular. Four examples of recent projects are provided below, which would be of interest to students wishing to apply their biological and chemical skill base to drug discovery and delivery problems.
The formulation of drugs for delivery to the airways Ongoing studies seek to explore the mechanisms involved in the successful delivery of drugs from aerosol formulations, both pressurised inhaler devices and dry powder inhalers. A number of inhalers now contain more than one drug, for example a beta-2 agonist and corticosteroid combination used in the treatment of asthma and chronic obstructive airways disease. The presence of one drug affects the position where the other drug is likely to deposit in the lung. Projects are currently investigating the effects of particle characteristics, such as size and shape on the efficiency of delivery, whether from dry powder or pressurized devices.
Nitric Oxide Biology, Chemistry and Formulation
NO plays many different roles in the body. It stimulates vaso- and bronchodilation and is involved in neurotransmission and also host defense mechanisms. NO donor molecules are an important group of therapeutics and their role in a number of diseases is increasing. Projects in this field will be designed to suit the student's interests and strengths. Examples of projects include (but are not limited to) the evaluation of the enzyme kinetics of S-nitrosoglutatione reductase (GSNOR), investigation of the influence of corticosteroids on GSNOR expression in lung epithelial cells, and the development of a liposomal-based drug delivery system for the NO donor, S-nitrosoglutathione.
The effect of intestinal fluid composition on the bioavailability of drugs
In order for any drug to be absorbed into the body after oral administration, it first has to dissolve in the fluids of the gastrointestinal fluids. For poorly water soluble drugs this process can be the rate-limiting factor that determines its subsequent absorption profile. A biopharmaceutics classification system (BCS) is employed by regulatory bodies such as the Federal Drug Administration (FDA) to categorize drugs into groups. Drugs with low solubility and/or permeability across membranes can be particularly problematic to develop. Many of the current tests designed to determine the dissolution rate of drugs and their subsequent solubility are carried out using simple fluids such as acid or buffers. The object of these studies is to determine the influence of simulated intestinal fluids on the classification drugs. It is expected that using simulated intestinal fluids of increasing complexity might alter drug classification based upon solubility such that less time and cost is spent on drug formulation.
The synthesis of hepcidin analogues
Hepcidin, a peptide hormone which is predominantly produced by hepatocytes, has a major role in maintaining iron homeostasis in mammals. It acts as a negative regulator of iron entry into the systemic circulation from macrophages and duodenal enterocytes and provides the predominant mechanism for controlling plasma iron levels. In this project structural analogs of hepcidin will be synthesized to determine the pharmacophore. The synthesis will be carried out using solid phase chemistry and the molecules will be purified characterized by HPLC and MS. Finally the analogs will be biologically tested in a cell culture assay in-house.
