Lipid Nanoparticles Improve the Uptake of α-Asarone Into the Brain Parenchyma: Formulation, Characterization, In Vivo Pharmacokinetics, and Brain Delivery

Treatment of brain-related diseases is one of the most strenuous challenges in drug delivery research due to numerous hurdles, including poor blood-brain barrier penetration, lack of specificity, and severe systemic toxicities. Our research primarily focuses on the delivery of natural therapeutic compound, alpha -asarone, for the treatment of brain-related diseases. However, alpha -asarone has poor aqueous solubility, bioavailability, and stability, all of which are critical issues that need to be addressed. This study aims at formulating a lipid nanoparticulate system of alpha -asarone (A-LNPs) that could be used as a brain drug delivery system. The physicochemical, solid-state properties, stability, and in vitro and in vivo studies of the A-LNPs were characterized. The release of alpha -asarone from the A-LNPs was prolonged and sustained. After intravenous administration of A-LNPs or free alpha -asarone, significantly higher levels of alpha -asarone from the A-LNPs were detected in murine plasma and brain parenchyma fractions, confirming the ability of A-LNPs to not only maintain a therapeutic concentration of alpha -asarone in the plasma, but also transport alpha -asarone across the blood-brain barrier. These findings confirm that lipid nanoparticulate systems enable penetration of natural therapeutic compound alpha -asarone through the blood-brain barrier and may be a candidate for the treatment of brain-related diseases.