ABSTRACT
The challenge of delivering therapeutics to the central nervous system due to the restrictive nature of the blood-brain barrier (BBB) is a substantial hurdle in neuropharmacology. Our research introduces a breakthrough approach using microtubule-dependent transcytosis facilitated by novel aqueous compounds. We synthesized a series of red-emitting pyran nitrile derivatives. The molecular structure of compounds, photophysical properties, and water solubility were characterized. BBB permeability of BN1 was assessed in an in vitro BBB model. The transmembrane transport mechanism was next analyzed. The derivative was injected in the wild-type mouse for evaluation of brain penetration and biodistribution in the brain. We further investigated the potential of BN1-functionalized BBB-nonpenetrated silica nanoparticles for brain targeting. This compound demonstrated an ability to form endosomes within the phospholipid layer, thus enabling efficient penetration of the BBB via microtubule-mediated transcytosis, as evidenced in vitro model. This was further confirmed by in vivo experiments that BN1 displays the excellent BBB penetration and retained in brain parenchyma. Furthermore, BBB-impermeable mesoporous silica nanoparticle codelivery system markedly enhanced the transport efficiency to the brain in vivo by BN1-functionalized. These findings indicate that our designed aqueous molecules not only are capable of traversing the BBB but also serve as a viable new strategy for central-nervous-system-targeted drug delivery.
ABSTRACT
BACKGROUND: The fruits of Malania oleifera Chun & S. K. Lee have been highly sought after medically because its seeds have high oil content (>60%), especially the highest known proportion of nervonic acid (>55%). Objective of the Study. The objective was to explore the effects of different doses of Malania oleifera Chun oil (MOC oil) on the learning and memory of mice and to evaluate whether additional DHA algae oil and vitamin E could help MOC oil improve learning and memory and its possible mechanisms. METHODS: After 30 days of oral administration of the relevant agents to mice, behavioral tests were conducted as well as detection of oxidative stress parameters (superoxide dismutase, malondialdehyde, and glutathione peroxidase) and biochemical indicators (acetylcholine, acetyl cholinesterase, and choline acetyltransferase) in the hippocampus. RESULTS: Experimental results demonstrated that MOC oil treatment could markedly improve learning and memory of mouse models in behavioral experiments and increase the activity of GSH-PX in hippocampus and reduce the content of MDA, especially the dose of 46.27 mg/kg. The addition of DHA and VE could better assist MOC oil to improve the learning and memory, and its mechanism may be related to the inhibition of oxidative stress and restrain the activity of AChE and also increase the content of ACh. CONCLUSION: Our results demonstrated that MOC oil treatment could improve learning and memory impairments. Therefore, we suggest that MOC oil is a potentially important resource for the development of nervonic acid products.
