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Franziska Kopp, Stefan Polei, Karen Falke, Thomas Eickner, Niels Grabow, Martin Witt, Oliver Stachs, Rudolf F Guthoff, Tobias Lindner; Ultra high-field MR-Imaging of a biodegradable, subconjunctival drug delivery system – in vitro, ex vivo and in vivo examinations. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4104.
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© ARVO (1962-2015); The Authors (2016-present)
Drug delivery systems have gained increasing importance in managing chronic ocular diseases such as glaucoma. During the development of biodegradable drug depots, information about dimension and the degradation process is of high importance. In this study, we assess the suitability of ultra high-field MR-imaging (UHF-MRI) for the characterization of depot localization and degradation.
An in situ polymerizing drug delivery system, consisting of hyaluronic acid and the cross-linking agent ELA-NCO, an isocyanate-functionalized 1,2-ethylene glycol bisdilactic acid derivative, was investigated using UHF-MRI at 7 Tesla (Biospec 70/30, Bruker, Germany). In vitro measurements of the components, before and after polymerization, were conducted to establish optimal scan parameters. Ex vivo images after depot injection into the subconjunctival space of an enucleated pig eye were compared with hematoxylin and eosin (H&E) stained sections of the same eye. In vivo imaging and volumetric quantification of the drug depot were performed 3 and 12 weeks after injection into the subconjunctival space of a New Zealand White rabbit.
The individual components as well as the polymer mixture could be analyzed in vitro with an optimal signal-to-noise ratio, using proton-density-weighted sequences with TE/TR = 7/2000 ms. Distinctly different polymer morphologies were observed based on the progress of the polymerization reaction. Ex vivo measurements of the polymer depot in a pig eye with TE/TR = 42/4550 ms achieved an in-plane resolution of 100 x 100 µm. Correlation of the MRI data with H&E stained sections confirmed the localization of the depot between sclera and conjunctiva. In vivo imaging of the drug depot using T2-weighted Turbo RARE sequences (TE/TR = 70/5180 ms) yielded an in-plane resolution of 120 x 120 µm. Volumetric analysis revealed a 36 % reduction between 3 and 12 weeks after depot injection.
UHF-MRI can be used as a noninvasive imaging tool during the development of subconjunctival drug delivery systems. T2-weighted Turbo RARE sequences allow high resolution depiction of the polymeric drug depot and its distinction from surrounding ocular tissues. Biodegradation of the drug depot can be monitored and quantified using volumetric analysis, which provides valuable information for the study and adaptation of drug release kinetics.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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