Ocular release of timolol from molecularly imprinted soft contact lenses

The aim of this study was to evaluate "in vivo" the usefulness of molecular imprinting technology to obtain therapeutic soft contact lenses capable of prolonging the permanence of timolol in the precorneal area, compared to conventional contact lenses and eyedrops. Soft contact lenses (diameter 14 mm, center thickness 0.08 mm) consisted of N,N-diethylacrylamide (DEAA; main component of the matrix), methacrylic acid (MAA; functional monomer) and ethylene glycol dimethacrylate (EGDMA; cross-linker) were prepared by the conventional methodology (non-imprinted) or by applying a molecular imprinting technique using timolol as the template (imprinted ones). After washing and reloading, timolol release studies carried out in rabbits showed that the soft contact lenses made by the molecular imprinting method (34 microg dose) provided measurable timolol concentrations in the tear fluid for 2.0- and 3.0-fold longer than the non-imprinted contact lenses (21 microg dose) and eyedrops (doses of 34 and 125 microg), respectively. Furthermore, the area under the timolol concentration-time curve (AUC) was 3.3- and 8.7-fold greater for imprinted contact lenses than non-imprinted contact lenses and eyedrops, respectively. The timolol concentration of the eyedrops did not affect the precorneal residence time of drug significantly. On the other hand, timolol loading capacity of the contact lenses was improved by the molecular imprinting method; the sustaining of the drug levels in the tear fluid being proportional to the loading capacity of the contact lenses. These results indicate that imprinted soft contact lenses are promising drug devices able to provide greater and more sustained drug concentrations in tear fluid with lower doses than conventional eyedrops.