Surface modifications to control drug release from therapeutic ophthalmic lenses - SurfLenses

Project summary

Nowadays, most ophthalmic drug formulations are applied as eyedrops. Although this administration form is easy to use and well accepted by patients, it requires frequent applications, leads to significant drug losses (> 95%) and may cause undesirable side effects, due to the rapid drug absorption into the bloodstream. The development of more efficient drug delivery systems, that enhance the ocular bioavailability of the drugs, has been subject of an increasing interest in the last years and is regarded as a major advance in ophthalmic therapeutics. Among the several studied possibilities, soft contact lenses (SCLs) have deserved special attention due to their high degree of comfort, biocompatibility and prolonged contact with the eye. Drug soaked SCLs demonstrated to be more efficient than eyedrops, but still lead to short release times and are not commercially available. In order to enhance their drug loading capacity and to achieve a controlled drug release, various methods have been explored. These methods may be extended to other ophthalmic lenses - the intraocular lenses (IOLs) - due to the similarity of the constituent materials and functionality. The main objective of this project is to develop new efficient systems for the treatment of ocular diseases and post-surgical infections, based on the surface coating or modification of drug-loaded ophthalmic lens materials. Commercial SCLs, IOLs and newly synthesized lens hydrogel materials will be loaded with model drugs (e.g. fluoroquinolones, cefuroxime). Their surface will be modified/coated to create drug diffusion barriers which lead to a sustained release for an extended period of time. Tested methods will include crosslinking of the surfaces, coatings with layer-by-layer polyelectrolytes and/or with liposomes, and adsorption/grafting of specific molecules. These methods are particularly welcomed both by clinicians and industry, since they may be used in commercial lenses whose properties and production are already optimized. For the first time, the in vitro drug release kinetics will be investigated considering the tribomechanical effect inherent to eyelid sliding: a homemade apparatus allowing for simulation of tear flow and blinking will be used. Physical-chemical characterization of the hydrogels will be done to evaluate the changes caused by the surface modifications. Numerical modelling will be used to aid in the optimization of the novel delivery systems. In vitro and in vivo (with animals) biological tests will be also carried out. To achieve these purposes, an international multidisciplinary team of researchers from universities (Instituto Superior Técnico - PT, University of Coimbra - PT, University of Iceland - IS) and hospitals (Instituto de Oftalmologia Dr. Gama Pinto - PT, Instituto Oftalmológico Fernández-Vega – ES) will work in straight collaboration with industry (PhysIOL - BE, an experienced IOL manufacturer, and Altakitin - PT, which produces raw materials for medical applications, like chitosan). The project has the support of Bausch+Lomb UK (see page 5), which will supply commercial SCLs. The collaboration of the companies is fundamental for the definition of new research routes with economic viability and may have repercussions on technology transfer and on the future funding for the research centers. The participation of ophthalmologists of the two reputed Ophthalmological Institutes will be crucial for the discussion of the clinical relevance of the project outcomes and preparation of a pre-clinical validation plan. The development of a new concept for drug-delivering ophthalmic lens, besides being beneficial for improving the peoples’ life quality, comfort and working ability at long term, would lead to savings for healthcare system. Collaboration between partners would enhance their cooperation potential, expertise and competitiveness at European and global level.