(51g) Ophthalmic Antihistamine Delivery Via Recognitive Contact Lenses for Allergic Relief

The IL-4 driven TH2 cell response to allergens and the subsequent IgE secretion, results in mast cell and eosinophil degranulation. This prompts the release of inflammatory mediators such as the H1-receptor binding histamine. Pharmacological downregulation is possible by the local delivery of H1-antihistamines, resulting in decreased vascular permeability, bronchodilation and decreased exudation of effector cells. This work addresses the unmet need for the controlled release of histamine antagonists such as ketotifen fumarate on the surface of the eye to treat allergic conjunctivitis.

Treatment options for seasonal and perennial allergic conjunctivitis primarily consist of oral antihistamines (which provide only partial and delayed relief with potential systemic side effects) and topical treatments. Since ocular bioavailability of topical drugs is very poor (typically less than 7% is absorbed by the eye), a high dosage is needed which prohibits contact lens use. Controlling and tailoring the release of anti-histamines via novel recognitive contact lenses with significantly enhanced partitioning can solve these problems with increased bioavailability, less irritation to ocular tissue, and reduced ocular and systemic side effects. Controlled release by conventional soft contact lenses typically does not work due to a lack of sufficient drug loading. Enhanced drug partitioning in hydrogels can be achieved by configurational biomimetic imprinting (CBIP) techniques which involve the formation of a pre-polymerization complex between the template molecule and functional monomers with specific chemical structures designed to interact with the template by non-covalent chemistry.

Analysis of the transmembrane domains of H1 receptors provided the critical amino acid-histamine non-covalent interactions, and monomers of similar functionality were chosen. H1-NMR and C13-NMR titrations indicated the appropriate host-guest chemistry and aided the rational design of gels with optimized drug-polymer complexation. Polymer networks were synthesized in a temperature controlled non-oxidative environment using free-radical UV photopolymerization. Equilibrium binding isotherms demonstrate enhanced loading with a factor of 2 to 6 times increase in the partitioning of drug compared to conventional networks depending on polymer formulation and polymerization conditions. Dynamic binding studies showed that within 15 to 20 hours gels could re-load a significant percentage of maximum drug capacity. Dynamic release profiles under physiological conditions demonstrated that a viable therapeutic concentration of drug can be delivered at a constant rate for extended periods. Novel network design and synthesis, with a basis in current physiochemical components of commercially available hydrogel contact lenses, has a huge potential to affect the administration of a number of ocular therapies.