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Michael Bassett, Chuck Blizzard, Deepa Mulani, Peter Jarrett, Amar Sawhney; Pharmacokinetic Profile of Moxifloxacin in the Tear Fluid of Canines Delivered from a Hydrogel Punctum Plug. Invest. Ophthalmol. Vis. Sci. 2011;52(14):473.
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To demonstrate the sustained delivery of moxifloxacin from a hydrogel punctum plug in a preclinical animal model.
Moxifloxacin was encapsulated in poly (lactide-co-glycolide) microparticles which were suspended in a 4-arm polyethylene (PEG) derivative solution and mixed with a trilysine amine solution and injected into small bore tubing. The PEG and trilysine cross-link and entrap the microparticles in a hydrogel matrix which is subsequently dried and cut to 3.5 mm plug lengths. Plugs were inserted into the vertical canaliculus of nine beagles and tear samples were taken with wicks over a period of 15 days and analyzed for moxifloxacin concentration by HPLC/MS.
The moxifloxacin punctum plug is designed for sustained drug delivery via a combination of hydration and hydrolysis. The moxifloxacin is contained primarily in the PLGA microspheres and a smaller amount is dissolved in the hydrogel phase to provide a "burst" release immediately after insertion. The encapsulated drug is released at a slow rate over 10 days. Hydration of the plug via contact with tear fluid causes expansion to provide retention in the punctum plus hydrolysis of the PLGA microparticles initiating drug release.
The moxifloxacin PK profile in beagle tear fluid over time, as shown in Figure 1, demonstrates both the burst and sustained release of moxifloxacin following administration. The drug levels measured in tear fluid exceed the measured in-vitro activity against many clinical ocular isolates, as summarized by Stroman et al., 2005. The sustained release of moxifloxacin from the plug provides both time above the MIC and elevated drug concentration which are associated with bacterial kill (Zelenitsky et al., 2003; Visalli et al., 1997).
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