Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy

• Published in: Journal of biomedical materials research. Part A 2022-10, Vol.110 (10), p.1621-1635
• Main Authors: Maxwell, Courtney J., Soltisz, Andrew M., Rich, Wade W., Choi, Andrew, Reilly, Matthew A., Swindle‐Reilly, Katelyn E.
• Format: Article
• Language: English
• Subjects: alginate; Alginates; Alginic acid; Brain injury; controlled release; Corticoids; Corticosteroids; Crosslinking; Cytotoxicity; Damage; Decompression; Drug delivery; Drug delivery systems; Epithelium; Eye; Eye (anatomy); hydrogel; Hydrogels; Injury prevention; Methylene blue; Nerves; Neuroprotection; ocular drug delivery; Optic nerve; Optic neuropathy; Oxidative stress; Reactive oxygen species; Retinal pigment epithelium; Rheological properties; Scavenging; Steroids; Toxicity; Trauma
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.37412

Many disease pathologies, particularly in the eye, are induced by oxidative stress. In particular, injury to the optic nerve (ON), or optic neuropathy, is one of the most common causes of vision loss. Traumatic optic neuropathy (TON) occurs when the ON is damaged following blunt or penetrating trauma to either the head or eye. Currently, there is no effective treatment for TON, only management options, namely the systematic delivery of corticosteroids and surgical decompression of the optic nerve. Unfortunately, neither option alleviates the generation of reactive oxygen species (ROS) which are responsible for downstream damage to the ON. Additionally, the systemic delivery of corticosteroids can cause fatal off‐target effects in cases with brain involvement. In this study, we developed a tunable injectable hydrogel delivery system for local methylene blue (MB) delivery using an internal method of crosslinking. MB was chosen due to its ROS scavenging ability and neuroprotective properties. Our MB‐loaded polymeric scaffold demonstrated prolonged release of MB as well as in situ gel formation. Additionally, following rheological characterization, these alginate hydrogels demonstrated minimal cytotoxicity to human retinal pigment epithelial cells in vitro and exhibited injection feasibility through small‐gauge needles. Our chosen MB concentrations displayed a high degree of ROS scavenging following release from the alginate hydrogels, suggesting this approach may be successful in reducing ROS levels following ON injury, or could be applied to other ocular injuries.