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Jinsong Ni, Fan Xiang, Josh Rowe, Chris Huntington, Mohammed Dibas, John E Donello; MALDI-MS and Grid-MS Imaging Technologies to Study Ocular Drug Distribution of Brimonidine in Rabbits. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2079.
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The research goal is to utilize Matrix-Assisted Laser Desorption Ionization (MALDI)-Mass Spectrometry and an innovative Grid-Mass Spectrometry technology to study ocular drug distribution of brimonidine via topical ocular dosing and of brimonidine via intra-vitreal injection in rabbits.
In group 1, single topical ocular dosing of brimonidine (0.15%) in a water formulation at pH 7.0 was applied unilaterally (OD) to female New Zealand White (NZW) rabbits. In group 2, single intra-vitreal injection of brimonidine (1 mg/mL) was applied unilaterally (OD) to female New Zealand White (NZW) rabbits. At 0.5 hr and 2 hr post-dose, rabbits were sacrificed and both dosing (OD) and non-dosing (OS) eyes were enucleated and snap-frozen in a dry ice/ethanol bath. Eyes were sectioned into ~ 10 um slides for MALDI-MS imaging and ~100 um adjacent slides for Grid-MS imaging.
For topical ocular dosing of brimonidine (0.15%), both MALDI and Grid imaging show similar ocular distribution patterns while Grid imaging provide quantitative and more sensitive measurement (Figure 1). Brimonidine seems to be able to reach the posterior segment of the eye via trans-cornea route. Brimonidine has pKa of 7.8, which contains nearly 50% of neutral molecules and 50% charged molecules at pH 7.0. This might explain why brimonidine would reach to the back of the eye preferentially through trans-cornea route rather through peri-ocular route. The data also shows that it is possible to deliver biologically relevant drug concentrations to the posterior segment of the eye. In addition, both MALDI-MS and Grid-MS imaging display biologically relevant drug concentration at iris/ciliary body in the contra-lateral non-dosing eye (Figure 2). Since iris/ciliary body is the proposed target tissue site for IOP lowering effect, this may explain the observation of pharmacological effect in the contra-lateral non-dosing eye in rabbits. Finally, minimum drug concentrations were observed at posterior segment of eyes at contra-lateral non-dosing eye, which suggests non-systemic route of drug delivery to the posterior segment of the dosing eye.
MALDI-MS and Grid-MS imaging technologies are powerful tools to investigate ocular drug distribution in animals.
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