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|Title:||Extended Ocular Drug Delivery using Hyaluronic Acid-Containing Model Silicone Hydrogel Materials|
|Keywords:||ocular drug delivery;silicone hydrogels;contact lenses;extended release;hyaluronic acid;glaucoma;Biochemical and Biomolecular Engineering;Biomaterials;Polymer Science;Biochemical and Biomolecular Engineering|
|Abstract:||<p>While eye drops are a well-accepted and convenient method for ocular drug delivery, they exhibit significant limitations such as poor drug bioavailability, low ocular residence time, pulsatile delivery profiles in the tear fluid as well as the need for patient compliance. Silicone hydrogel (SH) contact lenses have been proposed as alternative ocular drug delivery systems due to their potential for targeted delivery to the corneal surface and high oxygen permeability. The ability of novel hyaluronic acid (HA)-containing silicone hydrogel materials to release timolol maleate (TM), an antiglaucoma drug, or ketotifen fumarate (KF), an anti-histamine administered for ocular allergies, was examined.</p> <p>The releasable wetting and the therapeutic agent were added to the pre-polymer mixture of the SH during synthesis through direct entrapment, while the reaction was performed by UV induced free-radical. The impact of the wetting agent on the swellability, surface wettability, optical transparency and <em>in vitro </em>drug release was studied.</p> <p>Simultaneous drug and wetting agent incorporation resulted in modified SH materials with slightly increased water content and significantly improved surface wettability. In addition, the optical transparency of these materials was not affected by drug loading. However, direct entrapment of HA decreased their optical clarity. <em>In vitro</em> release showed that TM was released over a 14 day period, whereas KF release lasted up to 36 days. For both therapeutic agents used in the current research, non-covalent entrapment of wetting agent and its MW did not significantly change the release kinetics, however the release rate of TM was slowed and controlled by the release of the HA, due to electrostatic interactions between the protonated TM and the anionic HA.</p> <p>The development of SH materials capable of simultaneously releasing a therapeutic and a wetting agent for an extended period of time and in a sustained manner can have a significant potential as extended drug delivery systems for the treatment of front of the eye diseases while also possibly providing comfort during wear.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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