(56d) Engineering Ocular Biomaterials to Incorporate and Controllably Release Diverse Molecules

Engineering contact lens materials to controllably release of a combination of diverse molecule species is the most effective method of treating ocular conditions. As a result, incorporation of intelligent controlled release techniques, such as molecular imprinting, into contact lenses and other ocular biomaterials has received increased attention within the ophthalmic field. Recently published work s have shown the high potential value of biomimetic molecular imprinting in controlling the mass release of hydrophilic templates of highly diverse molecular weight and functionality from hydrophilic materials. However, current commercially available contact lens materials can be composed of up to 70% hydrophobic content. Relatively little work has investigated the adaption of controlled drug release mechanisms into the hydrophobic sections of ocular biomaterials or demonstrated high degree of control over the mass release rate of highly hydrophobic templates. There is a high need for a better understanding of the application and adaption of intelligent release strategies, such as imprinting, into strongly hydrophobic and biphasic materials. To this end, selected hydrophobic templates including prednisolone and ibuprofen were incorporated into a molecularly imprinted silicone hydrogel contact lens formulations. Similarly, the mass ratio of methacrylic acid to prednisolone (MAA/Pred) and 4–vinylphenol to ibuprofen (4VPh/Ibu) were both varied between 0 and 3. Control over the release of each molecule from the imprinted lenses was demonstrated both individually and simultaneously. The physical properties of the lenses were evaluated and found to be adequate for lens usage. It was shown for the first time that adaption of molecular imprinting into each phase of the lens material lowered the average phase diameter of the lens, which was demonstrated to help maintain the physical properties of the lenses. In addition, the hydrophilic comfort agents, trehalose and 120 KDa HPMC, were incorporated into the hydrophilic sections. Acrylic acid (AA) was selected as the hydrophilic functional monomer. The ratio of acrylic acid to both hydrophilic templates (AA/TCA) was varied between 0 and 4. The average hourly release rates for each of the molecules from the imprinted lens (AA/TCA ~4; 4VPh/Ibu ~ 2; MAA/Pred) were 44 μg trehalose/hr, 25 μg 120 KDa HPMC/hr, 6.5 μg ibuprofen/hr, and 3 μg prednisolone/hr. Trehalose was incorporated to provide high initial comfort for the first 6-10 hrs. Trehalose release was complete in approximately 10-12 hrs. The other templates released well beyond the 24 hour duration of wear for the lenses. Application of controlled release strategies simultaneously within different phases fully exploits the potential of drug-eluting lenses.