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Graphic element Research > Growth > Research projects > Previous projects > New Products and Materials > Life-saving drugs right on target
Graphic element Life-saving drugs right on target
     
 
In recent years, protein-containing (proteic) drugs such as alpha interferon have become a very important class of therapeutic agents, especially in the treatment of cancer and viral diseases. Unfortunately, due to their rapid removal from the bloodstream, they have to be administered in exceedingly high doses in order to maintain acceptable therapeutic levels. This can cause toxic side effects which in some cases prove incompatible with the therapeutic treatment. The object of this Brite-EUram project BE-7052 was to develop novel polymeric matrices suitable for use in nanocapsule delivery systems for channelling proteic drugs directly to specific organs.
 

Traditional drug treatment involves the introduction of substances into the bloodstream, which then circulate through the entire body in search of their target organs - a rather hit-and-miss approach. More recently, drug delivery systems have been developed based on the principles of antigen-antibody interaction, whereby specific molecular forms are recognised and taken up selectively by only specific organs. Such 'smart' systems improve the therapeutic indices of drugs immensely, allowing a significant reduction in both therapeutic dosages, side effects and health-care costs.
This project focused on the production of nanocapsule delivery systems from biodegradable and bioerodable polymers with well-balanced hydrophilic/hydrophobic characteristics. These were found to be best suited to the loading of proteic drugs and to the targeting of specific biochemical receptor sites. The targeting ability of synthetic nanocapsules, that is their ability to deliver their contents to specific sites within the body, depends to a large extent on their surface characteristics, which have to be carefully selected and designed.

Methodology

Prior to the preparation of the polymeric systems, toxicological screening and selection of the best-suited materials were carried out. Hybrid combinations of synthetic and natural polymers appeared extremely well suited to incorporating peptide and proteic drugs in desirable doses and were very versatile with respect to the production of nanocapsules.
Nanocapsules were produced displaying good dimensional and shape uniformity, morphological and physical integrity and suitability for pharmaceutical processing into injectable dosage forms. The manufacturing process, via a simple and novel a laboratory-scale procedure, can be easily scaled up for industrial-scale production. Surface modification was then carried out to impart targeting attributes through three-dimensional molecular dynamics modelling.
The prepared hybrid mixes, the individual components and the finished nanocapsules themselves were all found to be substantially safe in preliminary in-vitro and in-vivo toxicology studies. Further test results, such as those from the biodistribution of soluble radiolabelled nanocapsules, indicated that the prepared systems, once injected into the blood stream, targeted the hepatocyte receptors - that is, the elective targeting site.
Kinetic studies on the release of active components or mimicking proteins carried out on nanocapsules under different conditions showed the systems to be of the prolonged-release type, with a satisfactory life time in the blood stream and maintenance of good activity levels. Further clinical testing is now under way to confirm the safety of these delivery systems.

Implications and benefits

The project partners describe the new treatment as intelligent nanocapsules for targeting the delivery of proteic drugs for treating cancer, hepatitis C and other socially paramount diseases. A significant increase in the therapeutic index of powerful protein drugs and the ability to target specific organs will mean a great improvement in clinical therapy, improving quality of life for patients, reducing side effects and, of course, significantly reducing both social and medical expenses.
The use of such systems could be beneficial in a wide range of pharmaceutical applications outside of those already mentioned. For example, their use in radiotherapy would allow the reduction of dangerous isotopic dispersion throughout the body. Finally, the increasing replacement of synthetic drugs by natural protein-based ones could lead to a reduction in environmental pollution by the pharmaceutical industry.

Follow-up research

The potential global market for human leukocyte alpha interferon has been estimated at about 300 million euro over the next ten years. Further estimates show a competitive product of the type described obtaining a 7 to 10% share representing about 30 million euro over the same period.
The follow-up research ongoing at the Istituto Sierovaccinogeno Italiano SpA and the University of Pisa, is aiming to refine and standardise production procedures for nanoparticles suited to the administration of alpha interferon and other drugs.

Cordis RCN: 23142
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