Servicio de Información Comunitario sobre Investigación y Desarrollo - CORDIS

Final Activity Report Summary - CORDDS (Controlled Release Drug Delivery Systems)

The controlled release of drugs to patients by use of innovative materials can reduce the side effects of many drugs, allowing the active ingredient to act only under certain conditions and over a controlled time span so that the drugs can be administered to the patient less frequently, interfering less with their quality of daily life. The fellow went to work with Prof. Robert Langer to develop the ability to rationally design materials with real applications in the pharmaceutical world. Thus, during this fellowship, several different studies in polymeric, hydrogel and micro- and nanoparticle biomaterial areas were conducted:
1) The development of injectable in situ crosslinking gels synthesised from polysaccharide polymers, mainly, cellulose, hyaluronic acid and dextran based polymers. These gels were then tested for several different applications - for local antifungal therapy, cartilage regeneration and as injectable bone cements.
2) The improvement of the mechanical properties of hydrogels by the synthesis of elastomeric polymers from a variety of monomers, xylitol, maltitol, sebacic acid, etc.
3) The application of contact lenses as ocular delivery vehicles for an antifungal drug, econazole, with Massachusetts Eye and Ear Infirmary, Harvard Medical School.
4) A collaborative study was developed with a Spanish group from the University of Zaragoza, examining the antifungal properties of silver zeolites against Candida Albican fungi.
5) Despite their popularity as a new and innovative class of biomaterials in academic research, mesoporous silica nano- and micro- particles was exposed to exhibit high toxicity at certain doses.

The most important scientific contribution made was the note of caution published by the fellow on the use of mesoporous silicates in vivo for biotechnological applications. Unfunctionalised mesoporous silicates of particle sizes 150-4000 nm exhibit benign local biocompatibility but considerable systemic toxicity. This toxicity appears to result from the particles themselves and not from any contaminants or degradation products. These findings suggest that biomedical applications of mesoporous silicates should be explored in the context of modifications to reduce toxicity.

As a materials scientist, this project enabled the fellow to realise the complexity of developing innovative biomaterials for drug delivery applications. Factors such as controlled drug release (at the correct rate, in the correct location in the body), drug stability, mechanical strength, route and ease of administration, basic biocompatibility and biodegradation rates are difficult to optimise all at once. The biological pathways that foreign bodies interfere with, especially with particles or degraded biomaterial on the nanoscale, are not well understood. This project has encouraged the fellow to continue her research in this area and strive to continue to develop innovative materials, addressing all of these issues thoroughly.

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