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Charles D. Blizzard, Peter Jarrett, Amar Sawhney, Abbe Miller, Art Driscoll, Michael Bassett, Leslie Jost; Effect of Sustained Release Travoprost Delivered from a Punctum Plug on In Vivo Miotic Activity over 13-Weeks. Invest. Ophthalmol. Vis. Sci. 2012;53(14):506.
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To evaluate the effect of sustained release travoprost administered via a hydrogel punctum plug on in vivo miotic activity in the dog iris sphincter muscle contraction model.
Travoprost encapsulated in polylactide microparticles (PM), was suspended in a multi-arm PEG precursor solution and injected into small bore tubing prior to cross-linking. The travoprost in PM/hydrogel matrix was dried in the tubing and cut into plugs. The travoprost plugs were inserted at Day 0 into the inferior canaliculus of the right eye of 12 beagles and the contralateral left eye served as a control. A pupil pen light with gauge and a ruler was used to measure pupil diameter over 13-weeks. Average pupil diameter and standard error was calculated for each group per time point.
Upon insertion, the plugs hydrate and expand in diameter and shrink in length to provide retention. The microparticles then slowly degrade and release the travoprost into the tear fluid. At time zero, as shown in Figure 1, prior to plug insertion there is no apparent difference in pupil diameter between the treatment and control eyes. As the drug is released and it penetrates into the eye at sufficient levels, the dog iris sphincter muscle contracts thereby achieving in vivo miotic activity as demonstrated by the difference in pupil diameter compared to the contralateral control eye over a period of 13-weeks.
In canines, prostaglandin F2-alpha drugs (e.g. travoprost) when applied as eye drops stimulate and contract iris sphincter muscles. This in vivo miotic activity has been used as an experimental model to monitor potency and pharmacodynamic response. The results of this study demonstrate that travoprost delivered into the tear fluid from a hydrogel plug retained in the canaliculus can provide an extended duration pharmacodynamic response in a well established animal model.
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