Abstract
Lawsone methyl ether (LME) is an naphthoquinone compound that is derived naturally. Due to this compound’s properties of being an antioxidant, anti-inflammatory and neuroprotective agent, LME has been of interest for use in treating neurological disorders. However, LME’s ability to treat neurological disorders is limited by poor aqueous solubility, low bioavailability and its limited ability to cross the blood-brain barrier (BBB). This research focuses on developing a new formulation of LME that is a nanoformulation in order to deliver the drug to the brain more effectively and to enhance the neuroprotective properties of the drug. Nanoparticles that contain LME were formed from a suitable biodegradable carrier system that was evaluated based on the size, polydispersity index, zeta potential, encapsulation ratio and release profile of the drug. The optimized nanoparticles had a nanoscale size; exhibited high drug-loading efficiencies; and had sustained-release profiles, which resulted in the efficient delivery of LME across the BBB. In vitro studies showed that the nanoparticles could be taken up into cells better than free LME, and the nanoparticles reduced oxidative injury to neurons that were subjected to oxidative stress. Animal studies showed that LME accumulated in the brain more effectively when delivered via nanoparticle compared to free LME and that LME delivered via nanoparticle had improved neuroprotection due to decreased neuroinflammation, decreased production of reactive oxygen species and improved maintenance of neuronal integrity.