Hydrogel Based Therapeutic Delivery System for Peripheral Neuropathy
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Hydrogel Based Therapeutic Delivery System for Peripheral Neuropathy

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Abstract

Peripheral neuropathy is nerve damage that stimulates neuropathic pain, a type of chronic pain resulting from sensory nerve damage in the peripheral nervous system. This disorder is untreatable and is expected to rise due to the aging of the global population, increased rates of diabetes mellitus, and improved survival of cancer patients after chemotherapy. Proposed treatment for this condition includes competitively inhibitors of TNF-α with therapeutics such as etanercept. However, side effects of systemic delivery of therapeutics such as etanercept negatively impact immunity throughout the body. To locally deliver a protein like etanercept, alginate hydrogel has been used in the past; however, calcium ions that are used to crosslink the hydrogel have been shown to induce an inflammatory response. One way to circumvent high calcium concentration is to dope another hydrogel with agarose with alginate to produce composite gels. Here we study the effects of protein therapeutic loaded agarose-alginate (AgAl) hydrogels for the delivery of etanercept to a peripheral nerve. In vivo biocompatibility experiments show that AgAl hydrogels do not stimulate the immune response seen by alginate hydrogels. AgAl was found to have a controlled release of fluorescently labeled etanercept by anomalous (non-Fickian) transport. Scanning electron microscopy (SEM) reveals 1.5 % weight by volume AgAl hydrogels with 0.08 mM etanercept have pocket-like framework with an average diameter of 27 ∓ 7 μm. Finally, an in vivo pain model for the delivery of etanercept with 1.5 % AgAl hydrogel show that p38 expression was reduced indicating that AgAl may be a suitable hydrogel for protein therapeutics delivery to peripheral nerve for treatment of peripheral neuropathy.

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This item is under embargo until September 11, 2023.