The 5th United Kingdom and Ireland Controlled Release Society Symposium On:
"Polymeric Drug Delivery into the New Millennium"

8th January 1999, Aston University School of Pharmacy

Around 150 delegates from all parts of the U.K, from academia and industry, were welcomed to the 1999 UKICRS meeting at Aston Pharmacy School by the meeting organisers, Dr Saghir Akhtar and Dr Allan Coombes. Professor David Billington Head of the School of Life and Health Sciences at Aston University drew attention to the meeting venue. Birmingham's location in a region steeped in history, the city's manufacturing traditions, the exciting urban regeneration programme and the growth of new hi-tec industries. Professor Billington hoped that the attractions of Birmingham as a conference venue would bring the International CRS Symposium to the city in the next decade.

Professor Clive Wilson performing his last duty as Chairman of the UKICRS before handing over to Dr Tony D'Emanuele recounted some of the history of the CRS. The society was conceived in 1973 to represent members in the agrochemicals sector and has expanded to incorporate controlled delivery of pharmaceuticals, cosmetics and agriculture/veterinary applications. The CRS and its influence continue to grow : 1500 delegates attended the 1998 International Symposium in Las Vegas and strong links exist with the AAPS and BPC. The aim of UKICRS to develop contacts with organisations in related scientific areas was shown this year by the high attendance of delegates from the biomaterials field and the inclusion of a keynote Institute of Physics and Engineering in Medicine/UKICRS lecture on polymers for tissue repair.

The scientific session was opened by Professor Etienne Schacht from the University of Gent, Belgium. His talk on "Biodegradable Polyphosphazines for Biomedical Applications' clearly conveyed the versatility of this class of polymers in that the possible physical forms range from water soluble polymers, to hydrogels, elastomers and solids and the degradation rates (due to hydrolysis) are controllable from weeks to months. Blending of polymers and the incorporation of depsipeptide side groups in the polyphosphazine (PPZ) chain enables fine tuning of degradation characteristics. Controlled drug delivery had been achieved using 'reservoir or matrix--type' systems (for Mitomycin C) and polymer-drug conjugates. Long-circulating colloidal delivery systems were also feasible since PPZ nanoparticles, surface modified using PEO-PPZ conjugates, have shown reduced RES uptake after intra-venous administration.

Professor Neil Graham from the University of Strathclyde discussed controlled drug delivery from polyurethane/PEO hydrogels which can be designed to swell in aqueous environments under pH control. The hydrogels, produced by radiation crosslinking of PEO/PU polymers, can be produced as nanogel or microgel-structured particulates for further processing into coatings or drug-containing matrices for solid dosage forms. Drug release profiles can also be adjusted to provide constant delivery rates over a required timescale and the hydrogels allow controlled release of high and low molecular weight actives. One of the earliest commercial applications of the technology involved controlled delivery of pro ûstaglandin E2. Current research is exploiting non-water soluble and water soluble hydrogels for drug delivery, the latter form providing a promising material for controlling the release of protein therapeutics.

Dr Julian Blair of Quadrant Healthcare described the company's novel group of oligosaccharide ester derivative (OED) glass-formers for oral and pulmonary delivery of pharmaceuticals. These materials are welcome additions to what is still a relatively small number of options for controlled drug delivery (cf polylactides, polyorthoesters, polyanhydrides). The active is encapsulated in an amorphous OED matrix and released by a composite mechanism involving diffusion and controlled devitrification of the matrix. Drug release profiles can be varied by OED selection, control of formulation technique, particle size, drug loading and excipient composition. Drug loadings in excess of 40% w/w are achievable and drug release can be sustained over hours or days.

Lunch and poster viewing extended over 2 hours to allow adequate time for consuming, at leisure, an excellent meal, for appreciating the 40 posters on display and enjoying the social occasion which has become an integral part of the UKICRS national meetings.

The afternoon started with a joint Institute of Physics and Engineering in Medicine/UKICRS lecture : 'Biological recognition of synthetic and natural polymers in wound healing '. Professor Jeffery Hubbell from the University of Zurich presented a fascinating account of biomimetic approaches to material design for medical applications. In particular, much attention is currently being directed towards manipulating cell adhesion in both two and three dimensions in order to reduce specific adhesive interactions (eg blood platelets with cardiovascular implants), to target the adhesion of particular cell types (eg endothelial cells) and to induce specific adhesion-related cellular responses (eg migration of smooth muscle cells). Hydrogels formed by in situ photopolymerisation of PEG-based methacrylate macromers, for example, have been surface modified using bioactive peptides to promote adhesion of cell types desirable in wound healing. Biomimetics was also directing research in the area of enzyme-degradable materials which allow cell penetration after breakdown by locally active proteases such as plasmin, collagenase and elastase. Biomimetic signalling effects have also been incorporated into biological materials (such as fibrin) by using bi-domain peptides to influence their properties and biological function. One segment provides attachment to the fibrin matrix, the second (eg RGD cell adhesion sequence) supplies the required bioactive property.

The first lecture of the session on 'Polymers for CNS delivery' was presented by Professor Henry Brem from John Hopkins University School of Medicine Carmustine (BCNU)-impregnated polyanhydride gliadel implants for brain tumour therapy is the first new therapy to be approved by the FDA in 23 years. The wafer implants are implanted directly at the site of tumour resection and provide high local concentration of drug with minimal system toxicity. A linear dose response has been measured, with a drug loading of 20% proving to be the optimum dose. The success of the delivery system in improving survival of patients treated for gliomas, both at initial presentation and recurrence, indicates an important role for local delivery of other therapeutic agents such as cytokines, immunotoxins and anti-angiogenesis agents.

Dr Saghir Akhtar from Aston Pharmacy School continued the theme of CNS drug delivery with a talk on 'Sustained Polymeric Delivery of Antisense Nucleic Acids to the Brain'. The potential use of Ribozymes to specifically cleave the RNA component of the tumour-associated ribonucleoprotein, telomerase was presented. Other studies suggested that implantable biodegradable polymer formulations present an attractive strategy for improving site-specific delivery of antisense molecules within the brain.

The concluding lecture of the scientific session was delivered by Dr Adam Smith from Oxford University on the subject of 'Localised delivery to the cerebral cortex using Elvax slices : reversible silencing of intrinsic activity'. Sub-dural implants of Elvax polymer giving sustained release of the GABAA receptor agonist muscimol were used to achieve inactivation of cortex over a period of weeks or months so as to identify behavioural consequences. Autoradiographic tracing revealed a highly localised distribution of muscimol directly beneath the implant. Within 2 hours of implantation, no visual cortical responses were recorded throughout the 1500 µm depth of the underlying cortical layers. This level of functional blockade could be maintained for 6 weeks and was reversible; normal cortical responses could be recorded within 9 hours of implant removal.

A highly enjoyable and stimulating meeting was drawn to a close by the Chairman of UKICRS, Professor Clive Wilson who commented on the fascinating options for polymer controlled drug release which had been presented by the speakers and poster exhibits. The high standard of work and quality of presentation made judging of the posters extremely difficult this year "and the final choice was made from five excellent submissions. Julia Nwachuku from the Department of Pharmacy and Pharmacology at Bath University was awarded one of the £500 prizes for her poster on 'Gene transfer using a bifunctional peptide comprising a membrane translocating sequence coupled to a cationic DNA-binding domain'. Amelia Petch from Aston Pharmacy School won £500 for her poster on 'DNA chip technology as a novel technique for designing effective antisense oligodeoxynucleotides against the epidermal growth factor receptor mRNA'. The prizes will assist Julia and Amelia to attend the 1999 International CRS Symposium in Boston.

Finally the committee of UKICRS wishes to thank elan Pharmaceutical Technologies, Pfizer Central Research, ZENECA Pharmaceuticals and Skye-Pharma for their generous sponsorship which helped to ensure the high quality of the 1999 meeting.

A. Coombes