The speakers and hosts of the London Meeting. From left to right: Prof. Daan Crommelin, Prof. Helmut Ringsdorf, Dr. Gillian Francis, Prof. Jindrich Kopecek, Prof. Lisbeth Illum, Prof. Ruth Duncan, Dr. Clive Roberts, Prof. Tony Moffat, and Dr. Duncan Craig.
The second UK Controlled Release Society symposium, superbly organised by Dr. Duncan Craig, was held in January at the School of Pharmacy at the University of London. Over 150 participants attended from France, Germany, Holland, the United Kingdom, and the United States. Professor Sandy Florence, as Dean, welcomed the attendees to the School of Pharmacy and introduced Professor Ruth Duncan, the current chairperson of the UKCRS. She explained that the society had been set up in 1994 as a branch of the Controlled Release Society. Its aim was to further the internationalisation of the parent society and to act as a focus for the study and development of controlled release technologies within the UK. Professor Duncan said these objectives were now being realised with day symposia and joint meetings with other pharmaceutical science groups. The UKCRS Committee were particularly pleased that the current President of the CRS, Professor Jindrich Kopecek of the University of Utah attended the meeting. He give a short speech on the activities of the parent Controlled Release Society and endorsed the role of local national groups such as UKCRS in encouraging scientific research and communication in this area. Professor Kopecek formally opened the science meeting which was organised into a number of sessions of invited keynote speakers, a few short contributed presentations and a large poster session.
The use of immunoliposomes to target cells in the body as a potential way of treating disease was outlined by Professor Daan Crommelin (University of Utrecht, the Netherlands). He explained that there were a number of barriers to targeting disease sites in the body. These barriers included the endothelial lining of the vasculature, the activity of macrophages and poor perfusion of the target tissue. Turning to the function of immunoliposomes, Professor Crommelin explained that they were liposomes with surface antibodies or antibody fragments. They had potential in diseases where the targets were known to be in the blood circulation or endothelial wall. Some of the areas in which immunoliposomes might be used were autoimmune diseases, certain cancers (where the cells were circulating in the bloodstream), clot dissolution, cardiovascular disease, and in liver diseases localised in hepatocytes. The concept of using macrophages in a technique called "target cell dragging" was discussed. The target cell itself was not recognised by the immune system but, on interaction with the immunoliposome, it became recognisable by macrophages and was consequently removed from the circulation or tissue. Target cells could thus be selectively "picked out" from the circulation. This technique had been tested in the laboratory against the malarial parasite in rats. Immunoliposomes also had potential in thrombolysis after acute myocardial infarction. Liposomes with tPA inside had been developed which "homed in" on plasminogen in the thrombus. Professor Crommelin suggested that this technique might provide a way round some of the undesirable side effects of conventional tPA therapy which resulted from its effects on plasminogen in the blood.
Dr. Gillian Francis (PolyMASC and Royal Free Hospital, London) described methods to provide better attachment of polyethylene glycol (PEG) to therapeutic agents. There was considerable interest in using polymer-drug conjugates as a means of improving biological distribution and cellular uptake of drugs such as cytotoxic agents. There was a need to develop effective methods of attaching polymers such as PEG without compromising biological activity, toxicity or stability of the conjugate. Dr. Francis described a novel "pegylation" technique which had been used with various cytokines. These had demonstrated that improvements in both circulation half-life and bioavailability could be obtained. In particular, studies with GMCSF and erythropoeitin had shown that attachment of PEG rendered these agents "invisible" to the immune system. Furthermore, studies with liposomes had shown a decrease in hepatosplenic uptake and increased tumour localisation after pegylation of the liposome surface.
Professor Lisbeth Illum (Danbiosyst and University of Nottingham) discussed the difficulties associated with the delivery of peptides and proteins. These were challenging molecules for transmucosal delivery because they were large, water soluble and unstable. They did not easily cross biological membranes and were normally given by the parenteral route because they were difficult to administer by other routes. As an alternative, the nasal route of delivery was an option. Professor Illum argued that there were several advantages to this route, including high permeability compared with the gastrointestinal tract, a large surface area for absorption, high vascularity and a low first pass effect. In addition, the nasal route offered patient compliance and both pulsatile or sustained release preparations could be administered by this route. There were, however, a number of disadvantages to this route. The permeability of the membrane was poor, drugs needed to be able to penetrate the mucus layer in the nasal passage, degradation of the drug might occur and absorption was dependent on the location of the dosage form within the nose. Mucociliary clearance in the nose was also a problem, hence absorption might be enhanced by limiting this clearance. Starch or albumin microspheres had been used as delivery vehicles for this route, but the material of choice was chitosan.
Professor Karol Sikora (Hammersmith Hospital Medical School) said that the main stumbling block in gene therapy was the delivery of DNA to target cells. Delivery of genes could take place via physical methods or be virally mediated. Physical methods included microinjection, liposomal transfer, receptor mediated delivery and tissue injection. Viral methods included the use of a retrovirus, adenovirus or Herpes simplex virus. At present, nearly 80 per cent of gene therapy protocols used the retrovirus technique. Discussing the potential disease models that could benefit from gene therapy, Professor Sikora suggested that they would have to be life-threatening. Current targets for gene therapy were: immunodeficiencies, cystic fibrosis, haemoglobinopathies (e.g. thalassaemia), metabolic disorders, arthritis, HIV infection, central nervous system disease, muscle disorders (e.g. muscular dystrophy), cardiovascular disease (e.g. restenosis) and cancers. It was on cancer that most gene therapy had been focused to date. Professor Sikora described one of the potential approaches to gene therapy in cancer or for tissue specific drug release. The technique was termed "selective drug activation". It involved switching on certain transcriptional messages in a specific tissue or tumour. For example, if production of an enzyme involved in the activation of a prodrug could be switched on in a specific tissue or cancer, then this would produce selectivity in vivo. This type of technology was likely to be improved as the human genome sequence was mapped and genes expressed in normal tissues and tumour tissues could be identified.
Professor Helmut Ringsdorf (University of Mainz, Germany) discussed some of his work on supramolecular organisation and biorecognition. The focus of the research was to establish model systems which imitated the natural processes whereby molecules assembled into larger structures. It was the behaviour of these structures, and not the individual constituent molecules, which determined many biological processes, such as biorecognition. Viral docking had been studied using a monolayer lipid system which on interacting with a viral coat protein underwent a red to blue colour change. This had implications for the development of biosensors and other diagnostic tools, as well as demonstrating the degree of sophistication with which model systems to study these complex biomolecular interactions could be built.
There were also three excellent short contributed papers from young scientists within the UK. Dr. Jayne Lawrence (King's College, University of London) reviewed her recent work on the formulation of microemulsion-based gels. Dr. Clive Roberts (University of Nottingham) described how the atomic force microscope can be employed to study biomolecular structure, polymer surface degradation and the release of proteins of biodegradable systems. Dr. Andrew Lloyd (University of Brighton) described the novel use of biomimetic polymers based on phospholipid derivatives to improve the ocular compatibility of intraocular lenses.
There was a lively poster session over the lunchtime break with over 20 contributed posters from many of the major controlled drug delivery groups in the UK. Professors Crommelin and Kopecek were kind enough to adjudicate the posters and commented on the high quality through the session. Ana Fernandes (School of Pharmacy), Beverley Thomas (University of Bath) and Anya Hillery (University of Brighton) were awarded prizes as best posters. They will each receive £500 travel expenses towards attendance at the next CRS meeting in Stockholm in June 1997 and the parent society have agreed to waive their registration fees.
Overall, the meeting was a great success and much credit goes to Duncan Craig for his tireless efforts in organising the meeting. The UKCRS Committee would like to thank our industrial sponsors Cortecs Ltd, Ethical Holdings plc, Jago Pharma AG., Pfizer Central Research and Polymer Laboratories for their kind and generous support. We would also like to thank our UKCRS members for supporting this meeting so actively and look forward to seeing them at the next meeting in Manchester in 1997.
(Adapted in part from a report in the Pharmaceutical Journal)
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