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Ocular drug delivery from contact lenses: mimetizing the hydrodynamic conditions of the eye
Publication . Pimenta, Andreia; Valente, Ana; Pereira, José M. C.; Pereira, José C. F.; Filipe, Helena; Mata, José L. G.; Colaço, Rogério; Saramago, Benilde; Serro, Ana Paula
Effect of sterilization on drugs and lenses for ophthalmic applications
Publication . Topete, Ana; Oliveira, Andreia; Galante, Raquel; Bozukova, Dimitriya; Saramago, Benilde; Serro, A. P.
Diclofenac release from a silicon based contact lens material controlled by a chitosan/alginate coating
Publication . Filipe, Helena; Silva, Diana; Pinto, Luís F. V.; Henriques, José; Bozukova, Dimitriya; Saramago, Benilde; Serro, Ana Paula
Simulation of the hydrodynamic conditions of the eye to better reproduce the drug release from hydrogel contact lenses: experiments and modeling
Publication . Pimenta, A. F. R.; Valente, A.; Pereira, J. M. C.; Pereira, J. C. F.; Filipe, H. P.; Mata, J. L. G.; Colaço, R.; Saramago, B.; Serro, A. P.
Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In this work, a microfluidic cell was designed and used to mimic the continuous, volumetric flow rate of tear fluid and its low volume. The suitable operation of the cell, in terms of uniformity and symmetry of flux, was proved using a numerical model based in the Navier-Stokes and continuity equations. The release profile of a model system (a hydroxyethyl methacrylate-based hydrogel (HEMA/PVP) for soft contact lenses (SCLs) loaded with diclofenac) obtained with the microfluidic cell was compared with that obtained in static conditions, showing that the kinetics of release in dynamic conditions is slower. The application of the numerical model demonstrated that the designed cell can be used to simulate the drug release in the whole range of the human eye tear film volume and allowed to estimate the drug concentration in the volume of liquid in direct contact with the hydrogel. The knowledge of this concentration, which is significantly different from that measured in the experimental tests during the first hours of release, is critical to predict the toxicity of the drug release system and its in vivo efficacy. In conclusion, the use of the microfluidic cell in conjunction with the numerical model shall be a valuable tool to design and optimize new therapeutic drug-loaded SCLs.
Controlled release of antibiotics from vitamin E–loaded silicone-hydrogel contact lenses
Publication . Paradiso, Patrizia; Serro, Ana Paula; Saramago, Benilde; Colaço, Rogério; Chauhan, Anuj
Symptoms of bacterial and fungal keratitis are typically treated through the frequent application of antibiotic and antifungal eye drops. The high frequency of half hourly or hourly eye drop administration required to treat these indications is tedious and could reduce compliance. Here, we combine in vitro experiments with a mathematical model to develop therapeutic soft contact lenses to cure keratitis by extended release of suitable drugs. We specifically focus on increasing the release duration of levofloxacin and chlorhexidine from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS® contact lenses by incorporating vitamin E diffusion barriers. Results show that 20% of vitamin E loading in the contact lens increases the release duration of levofloxacin to 100 h and 50 h from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS®, respectively, which is a 3- and 6-fold increase, respectively, for the 2 lenses. For chlorhexidine, the increase is 2.5- and 10-fold, for the TrueEye™ and OASYS®, respectively, to 130 h and 170 h. The mass of drug loaded in the lenses can be controlled to achieve a daily release comparable to the commonly prescribed eye drop therapy. The vitamin E–loaded lenses retain all critical properties for in vivo use.

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Funding agency

Fundação para a Ciência e a Tecnologia

Funding programme

3599-PPCDT

Funding Award Number

M-ERA.NET/0005/2012

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