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Morgan V Fedorchak, Liza A Bruk, Nate Myers; Preliminary safety evaluation of a long-term, topical ocular drug delivery platform. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4755.
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Although topical eye drops are the most common treatment method for many ocular diseases, they are inefficient and inconvenient, often resulting in poor patient adherence and undesirable outcomes. Long-term injections can offer an alternative to eye drops, but are more invasive and have other risks. Previously, we reported on the efficacy of a novel, topical controlled release ocular drug delivery platform, and in this study we seek to expand upon those data with a preliminary safety evaluation.
The physical properties of the drug delivery system, which comprises a thermoresponsive hydrogel and biodegradable, drug-loaded microspheres, were characterized using the appropriate testing. This includes determination of least critical solution temperature (LCST), viscosity, solid fraction, and swelling ratio. Terminal sterilization was also tested prior to determining in vitro cytotoxicity on conjunctival and corneal epithelial cells using a live/dead assay. The likelihood of ocular irritation was determined using the hen’s egg test on chorioallantoic membrane (HET-CAM) and bovine corneal opacity and permeability (BCOP) test. In each case, sodium chloride solution was used as a negative control, and histological evaluation of bovine corneas was used to determine delayed effects, if any. Lastly, in vivo safety in a healthy rabbit model was determined by quantifying systemic drug levels and slit lamp examination.
In vitro characterization tests show favorable properties for use of this drug delivery system on the ocular surface. Viscosity was measured to be 0.248±0.005 Pa*s and LCST was 34.5°C, indicating suitability as a liquid drop that forms a solid depot. UV/Vis absorbance confirms opacity of the solid gel, a requirement for visibility during use. Solid fraction measurements over 28 days demonstrate that the gel is non-degradable over time. Results of irritation and cell viability studies demonstrate acceptable results, with no observable irritation during HET-CAM (Figure 1) and BCOP testing. Finally, systemic drug levels were not detectable and no irritation was noted during in vivo testing.
The results suggest that the materials tested are non-irritating and retain the necessary properties for their intended use. These data represent an important step toward translatability of the system.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
HET-CAM results (from top): negative control, gel, gel plus microspheres, positive control.
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