Abstract
Local drug delivery systems (DDS) have become a favourable approach for the treatment of numerous diseases. Biomedical imaging techniques such as ultrahigh field magnetic resonance imaging (UHF-MRI) offer unique insight into DDS biodegradation in vivo. We describe the establishment of a 7 Tesla MRI routine for longitudinal in vivo examinations of a subconjunctival DDS for the treatment of glaucoma in a rabbit model. In initial in vitro examinations the T2-relaxation times of the polymeric DDS components were assessed. Imaging of enzymatically degraded depot samples in vitro did not reveal changes in sample morphology or T2-relaxation time. Ex vivo investigations with an enucleated porcine eye showed good correlation of anatomical MRI and histological data. In longitudinal in vivo studies in rabbits, we repeatedly scanned the depot in the same animal over the course of 5 months with an in-plane resolution of 130 µm at scan times of less than 30 minutes. The degradation was quantified using volumetric analysis showing a volume reduction of 82% between 3 and 21 weeks after depot implantation. We have thereby demonstrated the feasibility of our UHF-MRI protocol as a non-invasive imaging routine for qualitative and quantitative, longitudinal evaluation of biodegradable subconjunctival DDS.
Highlights
Glaucoma encompasses a class of optic neuropathies characterised by progressive degeneration of retinal ganglion cells and concomitant irreversible vision loss
We recently developed a subconjunctival, in situ polymerising, biodegradable drug delivery system (DDS) eluting latanoprost for the treatment of primary open-angle glaucoma (POAG)
The signal intensity plot demonstrates that hardly any signal was detectable from the cross-linker ELA-NCO in the T2w TurboRARE sequence with the parameters used for imaging (AUCELA-NCO = 38.26; AUCHA(LP) = 790.3)
Summary
Glaucoma encompasses a class of optic neuropathies characterised by progressive degeneration of retinal ganglion cells and concomitant irreversible vision loss. Novel drug delivery devices like punctum plugs, inserts, and intraocular implants provide sustained drug release over an extended period of time They do not rely on daily patient participation for treatment success and are heavily pursued in medical research and development[9,10,11]. In a previous in vivo study in rabbits we used a surgical microscope for longitudinal monitoring of biodegradation and biocompatibility of the DDS12. This method was limited to imaging the surface of the drug depot and did not allow quantification of the degradation process. To test the developed imaging routine in longitudinal in vivo biodegradation studies, New Zealand White (NZW) rabbits received unilateral subconjunctival injections of the DDS. In vivo MRI measurements were performed in combination with biomicroscopic documentation over the course of 21 weeks following the injection
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