Europa reports that the TATLYS project is developing a system for targeted release of drugs to break down human blood clots. Biocompatible nanoparticles carry drugs to the exact location at an appropriate concentration.
The formation of blood clots in the circulatory system is associated with a range of serious medical conditions, including heart attacks, pulmonary embolisms, strokes and deep vein thrombosis. The main component of a clot is the insoluble protein fibrin. Treatment of vascular thrombosis involves the use of thrombolytic drugs that break up the fibrin, allowing the clot to disperse. The European market for thrombolytic drugs was estimated to be worth over €350 million in 2002, with an annual growth rate of 10%. Each year more than half a million patients worldwide receive thrombolytic treatment.
Professor Emo Chiellini of the University of Pisa, scientific co-ordinator of the TATLYS project, explains that thrombolytic drugs are powerful agents. “They can have serious side-effects, like causing haemorrhage, if they are given systemically. If you give them orally they will be partly broken down right away, so efficiency is reduced. But if you protect them with a nanoparticle, they may be delivered directly to the specific site of action. We use less material; the treatment is more cost-effective, and you get less side effects.”
The TATLYS project is linking new understanding of surface chemistry with the use of nanoparticles to offer spectacular advances in drug delivery. Nanoparticles containing urokinase are being prepared from biocompatible polymers on a laboratory scale. Simple proteins (oligopeptides) are modelled and synthesised to mimic the structure of specific sites on the fibrin molecules making up the clot.
Project partners will test various combinations of nanoparticles, oligopeptides and proteic drugs, to determine which offer optimal performance in terms of effective fibrin targeting and appropriate release of the drug. It will also be necessary to establish the stability and any possible toxicity of the nanoparticles.
The composition of the nanoparticles is critical, points out Professor Chiellini. “Knowing the structure of the site on the fibrin, we design a peptide that matches it – and the nanoparticle will bond to the site. Then the drug will be released from the nanoparticle by diffusion, degradation or physical erosion. Choosing different polymers to make the nanoparticles allows us to release the drug either in a short burst, or slowly over a period of time.”
The varied TATLYS technologies involve partners in two EU Member States, one associated state and three accession countries. The Research Unit of the National Interuniversity Material Science and Technology Consortium (INSTM) based at Pisa University, and Kedrion (also in Italy) provide scientific and administrative co-ordination. Among other partners are Polymer Laboratories in the UK, which produces polymers for the nanoparticles, and Novetide from Israel providing the peptides for surface-site labelling.
The project co-ordinators also acknowledge the value of complementary expertise contributed by incoming EU nations, and are encouraging an exchange of researchers between the partner institutes. The Polish Centre of Polymer Chemistry has specialists in biometic polymer synthesis, while the Czech Institute of Landscape Ecology brings experience in the formulation of polymers and magnetic nanoparticles. Scientists from the Slovak Institute of Experimental Physics use transmission electron microscopy to work on surface properties and dimensions of nanoparticles. And Vulm from Slovakia carries out toxicity testing to assess the viability of drug delivery systems.
At the end of the project, the partners hope to be able to set up procedures for preparing labelled nanoparticles, tested and ready to be scaled up. The knowledge should be available for exploiting the results, possibly through a new joint venture with a major industrial partner.
Support from the EU
As well as the financial support of € 2.14 million for the TATLYS project, Professor Chiellini notes the solid practical guidance received from the Commission services. “After 18 months, we had to prepare a technical implementation plan for the research. We had been creating wealth in terms of knowledge, but at this stage our advisor was helpful to us in pointing out the best way to go about commercial exploitation, by pointing out the risks and how to minimise them.”