Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy

Abstract

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.

Vancomycin-Loaded Gel Ocular Drug Delivery System for Treatment of Endophthalmitis

“…For the MTT assay, HRMEC cells were seeded in a 96-well plate at 5x10 4 cells/well in 200 µl of medium and incubated overnight in an incubator. Hydrogels prepared at different weights were sterilized by exposing to UV light for 1 hour [21]. Hydrogels (25, 50, 100, 200 µg/ml) were incubated with cells at 5% CO2 and 37°C for 24 hours.…”

Polymeric Gel Systems Cytotoxicity and Drug Release as Key Features for their Effective Application in Various Fields of Addressed Pharmaceuticals Delivery

“…Alginate gels are an effective means of delivering drugs capable of scavenging reactive oxygen species using a calibration needle. In [ 71 ], hydrogels based on calcium alginate containing the antioxidant methylene blue were studied. The hydrogels released more than 50% of the drug over 5 days followed by a slow sustained release of more than 80% of the drug.…”

“…Natural polymers are promising matrices for the manufacture of gel drug delivery systems because they are biocompatible and biodegradable in the human body. In particular, alginate hydrogels decompose by ion exchange [ 71 ]. Silk fibroin and collagen are degraded to form amino acids or peptides with a low molecular weight that are nontoxic to the body.…”

A New Era in Ocular Therapeutics: Advanced Drug Delivery Systems for Uveitis and Neuro-Ophthalmologic Conditions

“…Thus, targeting downstream mediators of neuronal damage is an appealing avenue for treatment. Maxwell et al (2021) developed injectable alginate hydrogels containing Methylene Blue (MB) to target the production of reactive oxygen species (ROS) contributing to RGC death in TON [ 63 ]. They observed a prolonged release of MB for up to 12 days compared to free MB.…”