Hyaluronic acid conjugated gold nanoparticles/chitosan/4-aminopyridine intranasal nanocomposites for myelin repair in multiple sclerosis.

Exploiting the therapeutic advantages of 4-Aminopyridine (4AP) in neurological conditions like multiple sclerosis (MS) are limited due to toxicity concerns and blood-brain barrier when administered through intraperitoneal or oral routes. Alternatively, intranasal delivery, which allows direct access to brain, would require 4AP to be encapsulated and stabilised. To meet this, a carrier based on hyaluronic acid (HA) conjugated to chitosan (C) with gold nanoparticles (G) for 4AP has been prepared (HA@G-C-4AP). Firstly, efficacy of G-C-4AP studied on C57BL/6 mouse model, where cuprizone was used to induce demyelination. Initially, significance of each nanocomposite component was studied; for example, G-C-4AP showed a T-maze alteration with significance at P < 0.01 when compared to induced alone group and promoted myelination as evidenced by increase in myelin markers, viz., myelin basic protein and proteolipid protein (P < 0.001, P < 0.01). Later, to prove higher localisation of nanocomposite in the presence of HA in brain tissue, HA@G-C (without 4AP) was encapsulated with fluorescent label 5-aminofluorescein (5AF) (HA@G-C-5AF), and brain tissue was observed through imaging system. Our studies indicate that HA-functionalised gold-chitosan nanocomposites can improve myelin repair owing to improved bioavailability of 4AP. Further long-term therapeutic studies on intranasal administration of HA@G-C-4AP nanocomposite in organoid and animal models are required for its use in clinical settings.