Drug delivery to the eye anterior chamber by intraocular lenses: An in vivo concentration estimation model

Abstract

Drug loaded intraocular lenses have been proposed as an alternative to the conventional post-cataract removal prophylaxis through topical drug administration, since the drug or combination of drugs released from the lenses are delivered directly to the target site. In this work, a mathematical model to estimate the concentration of drug released from such lenses in the eye aqueous humor was developed. To attain these estimated concentration profiles, partition and effective diffusivity coefficients for the specific lens material were obtained from standard in vitro release experiments. The model was validated by comparing the predicted aqueous humor concentrations with those obtained in in vivo studies where hydrophilic acrylic intraocular lens loaded with an antibiotic (moxifloxacin) were implanted in rabbits. Subsequently, other partition and effective diffusivity values were determined for levofloxacin, diclofenac and ketorolac in the same hydrophilic acrylic and in a second material, a silicone hydrogel. Predicted drug concentrations in the aqueous humor allowed an initial screening and evaluation of the most promising system for post-cataract removal prophylaxis, with the hydrophilic acrylic material presenting promising results, especially for moxifloxacin and diclofenac controlled release.

Keywords: Cataract removal postoperative; Drug delivery; Mathematical modeling.