Nose to brain delivery of Astragaloside IV by β-Asarone modified chitosan nanoparticles for multiple sclerosis therapy

Multiple sclerosis (MS), an autoimmune disease, has been considered an inflammatory disorder of the central nervous system (CNS) with demyelination and axonal damage. Although there are certain first-line therapies to treat MS, their unsatisfactory efficacy is partly due to the limited CNS access after systemic administration. Besides, there is an urgent need to treat MS by enhancing remyelination or neuroprotection, or dampen the activity of microglia. Astragaloside IV (ASI) bears anti-inflammatory, antioxidant, remyelination and neuroprotective activity. While its poor permeability, relatively high molecular weight and low lipophilicity restrict it to reach the brain. Therefore, β-asarone modified ASI loaded chitosan nanoparticles (ASI-βCS-NP) were prepared to enhance the nose-to-brain delivery and therapeutic effects of ASI on EAE mice. The prepared ASI-βCS-NP showed mean size of about 120 nm, and zeta potential from +19 to +25 mV. DiR-βCS-NP was confirmed with good nose-to-brain targeting ability. After intranasal administration, the ASI-βCS-NP significantly reduced behavioral scores, decreased weight loss, suppressed inflammatory infiltration and astrocyte/microglial activation, reduced demyelination and increased remyelination on a mice EAE model. Our findings indicate that ASI-βCS-NP may be a potent treatment for MS after nose-to-brain drug delivery.