Drug‐delivery contact lenses

Abstract

The prevalence of ocular chronic diseases, like those associated to diabetes (diabetic retinopathy, macular edema and glaucoma), has increased significantly in the last years. They affect quite negatively people's quality of life, leading to extremely high economic costs both for patients and society. Recent advances in pharmacotherapy have greatly improved their prognosis. However, the efficacy and safety of the treatments currently available are still a concern. Topical drug delivery (DD) is useful to treat diseases of the anterior segment of the eye, but new strategies are needed to increase drug's bioavailability, which is quite low, and to overcome the difficulties that e.g. elderly people face in topical administration. Regarding the posterior segment, the challenge is to reach the target tissues due to the eye's natural barriers. Topical treatments are generally useless in this case. Systemic administration requires large doses to achieve local therapeutic levels and may induce undesirable side effects. Intravitreal route provides direct access to the intraocular environment and is highly effective, but is rather invasive and may origin serious complications, such as endophthalmitis, retinal detachment, intravitreal haemorrhage and cataract. In BioMat Research Group of IST, and within the frame of ORBITAL and SOL projects, we are making efforts to develop and optimize new DD systems for the treatment of diabetic ocular diseases that use noninvasive routes and present sustained drug release capabilities, increasing the drug's bioavailability at the target tissues. We propose the use of soft contact lenses (SCLs) as DD vehicles, due to their high biocompatibility and prolonged contact with the eye. Being frequently replaced, SCLs may be used as drug reservoirs for continued treatments, not only of diseases of the anterior part of the eye, but also of the posterior, using innovative techniques that enhance the drug penetration in the eye. Although in the last years much research has been done on this type of devices, they are still not available in the market due to a number of reasons, such as the need of improving systems efficiency, the difficulty in transposing to industry the preparation methodologies, issues related with sterilization/storage or lack of in vivo and clinical tests. In our studies, we have used different strategies to increase the bioavailability of the drugs and achieve adequate drug release profiles. Besides applying coatings and molecular imprinting techniques, we investigated the formation of prodrugs and drug inclusion in nanostructures that protect them in the biological medium. The incorporation in SCLs of cell penetrating peptides (CPP) that increase drug's ability to cross the corneal epithelium and reach the back of the eye, also led to to promising results. Ex‐vivo tests and mathematical modelling were used to predict the biological performance of the drug‐loaded devices in vivo before performing tests with animal models. Finally, alternative sterilization techniques which allow to process such challenging systems were explored.The obtained results shall contribute for the development of new forms of treatment of ocular diseases that are more predictable, safe and effective, giving response to an unmet clinical need.