3rd UKCRS Symposium on "Controlled Drug Delivery - Current Perspectives and Future Horizons" - Manchester 1997

Meeting Report

The Third United Kingdom Controlled Release Society symposium on 'Controlled Drug Delivery: Current Perspectives and Future Trends' took place at the University of Manchester on the 6th of January 1997. The successful event was organised by Dr Antony D'Emanuele (University of Manchester) and was the first ever pharmacy related symposium to be broadcast live around the world via the Internet. Despite the adverse weather conditions, over 100 participants from the United Kingdom, North America and Europe were present at the meeting. The morning session was chaired by Professor Malcolm Rowland (University of Manchester) and Dr Marianne Ashford (Zeneca Pharmaceuticals, UK). Professor Rowland welcomed the attendees to the University of Manchester. He spoke of Manchester's long history of contribution to scientific progress. Professor Nicholas Peppas (Purdue University, USA), chairperson of the CRS Global Chapters Committee, officially opened the symposium with a message from the Controlled Release Society. Professor Peppas said that Professor Tsuneji Nagai (Hoshi University, Japan), president of the CRS, was delighted at the success of the UKCRS and their annual symposia. He gave a brief speech on the origin of the CRS and spoke of its continual growth and internationalisation. The Society now has members in over 85 countries. Professor Peppas was pleased to announce the recent establishment of local sections of the CRS in many countries around the world. He ended his opening speech by promoting the forthcoming CRS symposia and meetings in Buenos Aires, Athens, Tenerife, Italy, India and Stockholm.

Professor David Clarke (University of Manchester) was the first speaker of the day and gave an informative talk about his research into bioresponsive lipid based delivery systems. Professor Clarke described the limitations of current biosensing technology and said that few biosensor devices are considered reliable enough to be used in vivo as monitoring devices, or for feedback control. He emphasised that more intimate coupling of biosensors with release functions was required before useful, bioresponsive release systems could be developed. In nature, biomembranes are used to couple biorecognition events to a variety of effector functions. Professor Clarke explained that by integrating the biorecognition events used in biology and in vitro diagnostics into lipid bilayers, targeted molecular biosensors for screening and bioresponsive controlled release systems could be developed. He also discussed the use of biomimetic peptides to produce quantitative, bioresponsive release and transport of small molecules and proteins across lipid bilayers, and to bind reversibly to the variable and non-variable regions of immunoglobulins.

"Understanding Surface Macromolecular Interactions in the Design of Therapeutic Systems" was the title of Professor Martyn Davies' talk. Professor Davies (University of Nottingham) explained the importance of surface interactions in understanding the performance of advanced drug delivery systems at the molecular level. A number of advanced biophysical techniques have been developed to define surface phenomena. Professor Davies described two of these techniques, Atomic Force Microscopy (AFM) and Surface Plasmon Resonance (SPR), which he has used in his work. He explained that AFM was a relatively inexpensive technique and works in a similar way to a record player, in that it uses a very sharp tip to probe surfaces. AFM produces very high resolution 3-D images of molecular structures and surfaces and can provide useful data on molecular interactions. It can be used in almost any environment, requires little sample preparation, and can provide time-resolved data, therefore allowing molecular processes taking place in situ to be followed. AFM has been used successfully to image DNA-enzyme interactions, blood-clotting processes, release of protein-based drugs from polymeric drug delivery systems, the escape of a virus from its cellular host, the hydration of dextran molecules and phase separation in polymer blends. Professor Davies showed how the atomic force microscope could be adapted for measuring forces of dissociation between macromolecules e.g. biotin and streptavidin. He then discussed the technique of SPR and its use in investigating the adsorption of polymers to surfaces. Professor Davies ended his talk by explaining that by combining these techniques a greater insight into understanding molecular interactions could be gained.

Professor Nicholas Peppas returned to the podium to deliver his talk on the design of new biomaterials for drug delivery. Professor Peppas discussed the potential of many novel polymeric materials in a wide range of controlled drug delivery applications. He spoke about the use of novel pH or temperature-responsive grafted polymer hydrogels to achieve pulsed, "on-off" controlled peptide drug delivery. These "intelligent" hydrogels undergo dramatic swelling and collapse triggered by very small changes in the pH or temperature of its immediate environment. This swelling and collapse corresponds with increase or decrease in the mesh size of the polymer matrices, thus allowing control over the efflux of drug out of the hydrogels by manipulating the pH or temperature. Professor Peppas discussed the need to demonstrate that the swelling/collapse behaviour of the hydrogels is reproducible over several thousand cycles without polymer failure, and also to determine the biocompatibility of these novel biomaterials. Professor Peppas also expressed his interest in novel star polymers (dendrimers) and their applications to polymer therapeutics. He said that many of these star polymers have been shown to be non-toxic and that there was great potential in developing star polymers for controlled release applications. The structure of star polymers allow the expression of large numbers of functional groups in a relatively small volume. He explained that these functional groups could be used to immobilize enzymes.

Professor Ruth Duncan (University of London), current chairperson of the UKCRS, explained the role of the UKCRS in acting as a focus for the study and development of controlled release technologies in the UK and also to provide a forum for the exchange of information within the field. She expressed her delight at the high attendance at the symposium and thanked Dr Antony D'Emanuele for organising the event. Professor Duncan was optimistic about the future of controlled release technology in the UK and said that this was reflected in the high proportion of young scientists present at the meeting and also in the high standard of the posters on display. She said that although research into controlled release in the UK was primarily related to pharmaceutical applications, controlled release technologists working in other areas, such as agriculture, were more than welcome to join the UKCRS and take part in its activities. Professor Duncan said that she would be stepping down from her position as the chairperson of the UKCRS and that Professor Clive Wilson (University of Strathclyde) would be taking over as the chairperson. She also said that Dr Colin Pouton (University of Bath) and Professor Martyn Davies would be standing down from the UKCRS committee. Professor Duncan commended Professor Davies for all the hard work and effort he has put into setting up and running the UKCRS.

The poster presentations took place after lunch, and highlighted the many diverse areas that are currently being investigated in the field of controlled release drug delivery. Topics covered included anticancer agents, gene delivery, transdermal delivery, biodegradable polymers and novel hydrogels as drug delivery systems. A prize of £500 plus registration fee for the annual CRS conference that takes place in Stockholm this June was awarded to Sasa Dimitrijevic from the School of Pharmacy, University of London, and James Birchall from the Welsh School of Pharmacy, University of Wales, for the best poster presentations.

The first talk of the afternoon was given by Dr. Stephen Zale from Alkermes Inc., Massachusetts, and was titled, 'Polymeric Microspheres for Sustained Delivery of Therapeutic Proteins.' At present, therapeutic proteins generally have to be administered by frequent injections due to their low oral bioavailability and short half-lives. Dr. Zale talked about a system called PROLEASE, an injectable, microsphere-based, sustained release delivery system for protein drugs. Trials in humans have shown that this system is capable of sustaining release for up to 3 weeks. Dr. Zale discussed the techniques and problems that occur in the processing and formulation of this system, including the issues of protein integrity and stability during storage and injection.

It has always been a policy of the UKCRS to encourage the work and research carried out by postgraduate students and young scientists. To this end, there then followed three short talks given by young scientists from academic institutions over the country. The first, confidently presented by Dr. Ijeoma Uchegbu from the School of Pharmacy, University of London, discussed the uses of niosomes in drug delivery. Niosomes are non ionic surfactant vesicles, which have been found to be useful drug carriers in previous in vivo studies. However, these agents were found to be taken up by the liver. Dr. Uchegbu described in vivo studies performed with new niosomes formed from N-palmitoyl muramic acid and loaded with doxorubicin. These studies showed that these vesicles avoided liver uptake, and instead were predominantly taken up by the spleen.

The next talk was given by Susan Berill, a final year postgraduate student at the University of Manchester. Susan's talk was concerned with biodegradable polycaprolactone copolymer blends. Polycaprolactone is a biodegradable and biocompatable polymer, however, its hydrophobicity makes it unsuitable for implantable polymer-drug systems, as this is indicative of poor drug loading and release properties. Susan discussed the incorporation of a polyoxyethelene moiety to increase the hydrophilicity of the polymer blend, and as such, give rise to hydrolysis and enzymatic cleavage of the polymer, and allows the release of the drug.

The last of these 15 minute talks was given by Snjezana Stolnik from the University of Nottingham, and was entitled 'The Difference in Biological Properties of Poly(ethylene oxide) Coated Colloidal Carriers - Relation to their Physicochemical Properties.' Dr. Stolnik discussed how the adsorption of copolymers of polylactide-poly(ethylene oxide) onto colloidal drug carriers can reduce the problem of the colloid accumulating in the liver and spleen, whilst prolonging the circulation time in the blood. However, this effect is not obtained with polystyrene colloids The work presently being carried out aims to assess whether the observed differences in the biological performance are related to a difference in the adsorption behaviour of the polylactide-poly(ethylene oxide) on the surface of the colloids.

Dr Antony D'Emanuele from the University of Manchester gave the next talk on pharmaceutical information on the Internet. The Internet is a powerful information resource, which can provide pharmacists all over the world with the means to communicate with each other. Dr D'Emanuele talked about PharmWeb, a pharmaceutical and health information service, created by him, which has been accessed by over 110 different countries, and the UK servers alone have over 140,000 page requests each month. PharmWeb presents scientists and patients with the opportunity to search for material in sites specifically tailored for pharmaceutical needs, whilst also offering other services, including PharmWeb appointments, information on forthcoming conferences and events, mailing lists and on-line discussion groups for the exchange of information between readers.

Dr Anthony Phillips from Glaxo Wellcome finished off the day with an industrial perspective of gene therapy. There are over 4,000 diseases which have been identified as gene disorders, and gene therapy offers the potential to cure or reduce the effects of many of these. Dr Phillips discussed the issues that face the development of these products, such as cell targeting, manufacture at the scale required, and demonstration of safety to the regulatory authorities. He then went on to give examples of viral and non-viral based systems and briefly discussed their manufacture and the way in which they work. Dr Phillips left us with the message that he believes that the first gene therapeutic will be on the market early in the next millenium.

Overall, the day was thoroughly enjoyable, with a balanced diversity of subject matter, invoking much discussion. For that, we should thank the members of the CRS, the local organiser, Tony D'Emanuele, and all those who presented such stimulating posters and talks.

Written by Sai Kit Li and Samantha Watson

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