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Giuliano Guidi, Andrea K. Weeks, Heather Sheardown; Molecularly Imprinted Hydrogels with Hyaluronic Acid for Ocular Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2012;53(14):458.
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The use of eye drops for ocular drug delivery while convenient is inefficient and poses a risk of systemic side effects. Contact lenses with a well-documented history of use in the eye represent a promising alternative vehicle. The potential of a contact lens delivery system for the prostaglandin analogue, timolol maleate was investigated and the effect of factors such as material polarity, molecular imprinting and HA were analyzed to further understand the drug-hydrogel interactions which govern the release kinetics.
Two model lens materials were created based on combinations of dimethylacrylamide (DMAA), hydroxyethyl methacrylate (HEMA) and methacryloxypropyltris(trimethylsiloxy)silane (TRIS). The materials were prepared with and without the direct addition of 7.5 kDa hyaluronic acid at 0.1 wt% and timolol maleate at 0.3 wt% and cured under UV light. Molecular imprinting was accomplished and a subsequent uptake study was performed for two days using two solutions, one containing timolol in PBS at a concentration of 0.2mg/mL and another containing both timolol and hyaluronic acid in PBS at 0.2mg/mL. Release studies were then performed on the molecular imprinted materials using UV- spectroscopy to quantify release. Materials were also characterized by swelling and contact angles.
Release studies show that 90% of the release for both pHEMA/TRIS and DMAA/TRIS occurs within approximately 3 days and 2 days respectively. The pHEMA/TRIS materials show an average 25% increase in total drug release over the duration of the study in comparison to the DMAA/TRIS materials. The effect of imprinting yields a consistent trend with both timolol and HA imprinted materials independently showing increasing release and a compounded effect when materials are imprinted with both compounds simultaneously. The increase in uptake affinity associated with timolol imprinted materials is consistent with established literature, however, the effect of HA increasing drug release is a novel result.
It is evident the polarity of monomers, the ratio of their contribution and the nature of the therapeutic are all determining factor in uptake and release for these systems. Hyaluronic acid imprinting appears to affect the uptake and release of therapeutics regardless of its similarity to the target compound and this interaction requires further characterization.
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