期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 644, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2023.123351
关键词
Astragaloside IV; beta-asarone; Intranasal delivery; Multiple sclerosis; Remyelination
Multiple sclerosis is an inflammatory disorder of the central nervous system, and its treatment is limited due to poor CNS access of drugs. Astragaloside IV has potential therapeutic effects, but its delivery to the brain is restricted. Researchers have developed beta-asarone modified chitosan nanoparticles to enhance the delivery and treatment of astragaloside IV for multiple sclerosis.
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, beta-asarone modified ASI loaded chitosan nanoparticles (ASI-beta CS-NP) were prepared to enhance the nose-to-brain delivery and therapeutic effects of ASI on EAE mice. The prepared ASI-beta CS-NP showed mean size of about 120 nm, and zeta potential from +19 to +25 mV. DiR-beta CS-NP was confirmed with good nose-to-brain targeting ability. After intranasal administration, the ASI-beta CS-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-beta CS-NP may be a potent treatment for MS after nose-to-brain drug delivery.
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