(509e) Macromolecular Engineering in Silicone Hydrogel Contact Lenses for the Controlled Release of Multiple Small Molecules
AIChE Annual Meeting
Wednesday, October 31, 2018 - 1:42pm to 2:00pm
Contact lenses were prepared using a mixture of silicone macromer methacryloxypropyl terminated polydimethylsiloxane (DMS-R11), methacryloxypropyl-tris-(trimethylsiloxy) silane (TRIS), and dimethyl acrylamide (DMA). Crosslinking monomers ethylene glycol dimethacrylate (EGDMA) and polyethylene glycol 200 dimethacrylate (PEG200DMA) as well as functional monomers diethylaminoethyl methacrylate (DEAEM), and diallyldimethyl ammonium chloride (DADMAC). Ethanol was included in the pre-polymer formulation to help dissolve template molecules and create a homogeneous lens solution. Heavily prescribed post-cataract therapeutics including dexamethasone sodium phosphate (DMSP), diclofenac sodium (DS), and bromfenac sodium (BS) were selected as template molecules. Lenses were synthesized using UV photopolymerization with a free radical initiator. Release experiments were conducted using a poly-dimethylsiloxane microfluidic device possessing an inner chamber with an inlet and an outlet, and a radius of curvature of 9.00 mm Â± 0.1. To simulate physiological tear flow, release media was injected into the chamber at 3 Î¼L/min, while an outlet line removed fluid from the chamber. Lens optical clarity was analyzed by measuring percent light transmittance using a UV/Vis spectrophotometer.
Contact lenses synthesized in presence of template molecules showed higher binding affinity and loading capacity than lenses synthesized without template. Further investigation of release studies suggested that macromolecular memory sites extended the release of both template molecules. Lenses with memory were able to extend therapeutic release of DS and DMSP up to seven days while control lenses with no memory released 90% of their payload by two days. In this study, additional therapeutic was applied to the surface of lenses to allow for a release of 40% of the total payload within the first day before slowing to a rate of 5.4 Â± 0.6 Î¼g/day for DMSP and 8.6 Â± 1.0 Î¼g/day for DS. By changing the functional monomer to template drug (M/T) ratio, lenses could be tailored to release multiple molecules at controlled rates. The NSAID bromfenac sodium was released from two different engineered lenses. By increasing the M/T ratio from 3 to 25, therapeutic delivery duration increased from 14 days to 36 days. Synthesized lenses met the commercial standards for elastic modulus (~3.5 MPa) as well as optical clarity (>90% optical transmittance). Silicone hydrogels are biphasic, and thus contain hydrophobic groups on the surface. Lens surfaces were treated with a plasma coater in order to create a purely hydrophilic surface. In order to determine hydrophilicity, contact angle between water and the surface of the lens was measured and found to be ~16°, which meets the commercial standard of <49°
Results indicated that macromolecular memory can be used to create custom hydrogels that release at specific sustained rates. This is the first time significant control over release of multiple molecules with diverse functionality has been demonstrated from a single lens for the duration of wear. This technology has significant potential as a more efficacious and effective method of treating ocular ailments.