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Katelyn E Swindle-Reilly, Courtney J Maxwell, Andrew M Soltisz, Andrew Choi, Wade Rich, Matthew Aaron Reilly; Injectable Alginate Hydrogels for Traumatic Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2682.
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© ARVO (1962-2015); The Authors (2016-present)
Traumatic optic neuropathy (TON) is a common, untreatable injury resulting in blindness. Prior candidate treatments for TON do not address secondary injury mechanisms, namely the generation of reactive oxygen species (ROS). We hypothesize that by addressing these secondary mechanisms via an injectable drug delivery vehicle loaded with a ROS scavenger, methylene blue (MB), greater neuronal cell survivability can be achieved.
Alginate hydrogels were synthesized at various polymer and crosslinker concentrations using design of experiments. Hydrogels were formed by internal crosslinking with insoluble calcium carbonate and proton donor, D-glucono-lactone. Viscoelastic properties of hydrogels were characterized using dynamic shear rheology. The cytotoxicity and ROS scavenging ability of the hydrogels loaded with MB concentrations of 0.0, 0.05, 0.25, 0.50, 1.0, and 2.0 g/L were analyzed through MTS and DCF assays, respectively, on ARPE-19 cells. A two tailed student t-test was used for statistical analysis.
By varying components of the gels, a significant influence on complex shear modulus and gelation time were observed. Lower concentration (alginate and crosslinker) hydrogels corresponded to lower complex shear moduli whereas higher concentration hydrogels had higher complex shear moduli. Hydrogel swelling and MB release were analyzed. Hydrogels with low alginate concentrations had the most cumulative MB release (~90%); however, no hydrogel completely released all MB within the 12-day in vitro study, due to hydrogel degradation. Two formulations demonstrated excellent cell viability at >95% following 24 hr exposure compared to DPBS control. ROS studies showcased MB as an effective scavenger at concentrations 0.50 g/L and above in which cell viability was maintained ~50% following exposure to 600 µM H2O2. The presence of MB was also found to significantly increase cell survival in the presence of oxidative stress when loaded into low and high concentration hydrogels (p<0.01).
Our results are consistent with our hypothesis that by inhibiting ROS induced damage, higher cell survivability can be achieved. The proposed drug delivery system has the potential to improve upon the limited treatment options for TON. Given the in vitro drug release and biocompatibility results, these hydrogels have potential to deliver MB to protect against ROS. Future work will include long-term and in vivo validation studies.
This is a 2021 ARVO Annual Meeting abstract.
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