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Frances Lasowski, Giuliano Guidi, Heather Sheardown; Multivariate Statistical Analysis Examining and Modeling Drug Release from Contact Lens Materials. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5470. doi: https://doi.org/.
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Topical administration of eye drops remains the most prevalent method of delivering drugs to the eye. However significant loss and potential systemic side effects necessitates a more effective drug delivery method. Contact lenses represent an attractive option as an alternative vehicle for wide range of therapeutics. Namely, the use of a model contact lens delivery system for the ocular drugs timolol maleate, roscovitine and atropine were investigated. The effects of drug loading, material composition and presence of wetting agents were analyzed to further understand the drug-hydrogel interactions that govern release kinetics and critical material properties. However, due to the complex nature of these interactions, single variable analysis of the data is insufficient to predict of future trends.
Model lens materials were based on combinations of dimethylacrylamide (DMA), hydroxyethyl methacrylate (HEMA) and methacryloxypropyltris(trimethylsiloxy)silane (TRIS). The materials were prepared with and without roscovitine (0.5 wt%), timolol maleate (0.5 wt%) and atropine (0.5 wt% & 1.5 wt%). Others contained hyaluronic acid at 0.1 wt%. Release studies were performed into PBS solutions using UV- spectroscopy and HPLC to quantify release of each drug. Swelling, extraction and contact angle studies were done to characterize the materials. This information was compiled and inputted into ProMV, a multivariate analysis tool provided by Prosensus, Inc. This allowed for examination by both PCA (principle component analysis) and PLS (projection to latent structures).
Single variable analysis trends include greater total drug release from HEMA/TRIS materials than DMA/TRIS materials, greater release of timolol and atropine than roscovitine, and greater release with HA present. The figure shows sample release kinetics from various materials at different drug loadings. Despite these trends, it is difficult to see trends bridging all drug loadings and material compositions. With multivariate analysis, it is possible to see the design space and predict compositions and drugs that yield the preferred release kinetics and properties.
Contact lenses provide a feasible method to deliver a variety of drugs to various ocular tissues. The use of multivariate statistical analysis provides better modeling and creates a predictive model allowing optimization of future materials.
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