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Jennifer J Kang-Mieler, Wenqiang Liu, Anessa Puskar Tawakol, Kayla Rudeen, William F Mieler; Safety and Biocompatibility of a Biodegradable Microsphere-Hydrogel Drug Delivery System in Long-Evans Rats. Invest. Ophthalmol. Vis. Sci. 2020;61(7):322a.
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Recently we demonstrated that our biodegradable microsphere-hydrogel drug delivery system (DDS) is able to release of anti-vascular endothelial growth factors for over 6 months. Previously, we demonstrated that DDS materials and degraded byproducts were biocompatible in vitro. The purpose of this study was to investigate in vivo safety and biocompatibility of the DDS in Long-Evans rats.
Three healthy Long-Evans rats received 5 µl of sterile blank DDS (no active drug) intravitreal (IVT) injections into both eyes.Scotopic corneal electroretinography (ERG) was performed before injection (control baseline), at 2, 4, 8, 16, and 24 weeks after IVT injections. A-wave and b-wave maximal responses and intensity-response function were recorded to evaluate DDS’s effects on retinal function. Intraocular pressure (IOP) was monitored using TONO-PEN®XL throughout the study. Direct slit lamp ophthalmoscope and cSLO infrared module was used to examine the eyes at predetermined time points. At the end of study, hematoxylin and eosin (H&E) histopathology was performed to investigate possible chronic inflammatory responses.
The baseline maximal a- and b-wave amplitudes were 604±110 and 1113±231µV, respectively. The baseline half-saturation intensity (Naka-Rushton) of a- and b-wave were 5.01±2.59 and 0.013±0.001 sc cd s m-2, respectively. Significant decrease in a-wave amplitudes were observed at week 2 (28.92%), 4 (29.87%), and 8 (27.07%) after DDS injections (p < 0.05). This decrease was not significantly different from baseline at week 16 and thereafter. No significant changes in a-wave sensitivity were observed throughout the study compared to baseline. Although there was an initial 21.30% decrease in b-wave amplitudes at week 2, it was not significantly different from baseline thereafter. Significant changes of b-wave sensitivity were only observed within first month (p < 0.01). The average baseline IOP was 24.17±1.38mmHg, transient increase of IOP (p < 0.05) was found immediately after injections but recovered to baseline level after week 4. No morphological abnormalities and inflammation were observed during ophthalmoscopic examinations and histology.
The microsphere-hydrogel DDS is safe, well-tolerated and biocompatible in vivo. No long-term functional and morphological abnormalities were observed for the entire six months after IVT injection.
This is a 2020 ARVO Annual Meeting abstract.
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