Abstract
Celastrol is a promising anti-inflammatory and antioxidant therapeutic for diseases of the central nervous system involving chronic activaton of microglia, the main innate immune effector cells of the brain. However, celastrol exhibits low aqueus solubility and a narrow therapeutic index. Herein, we propose the use of nanodelivery systems (e.g. neutral and cationic PAMAM dendrimers and gold nanoparticles) for the efficient solubilisation and delivery of celastrol to microglia. We show significant decreases in inflammatory mediator release (e.g. nitric oxide) and inflammatory signaling (i.e. p38 inhibition) in LPS-stimulated microglia. Furthermore, gold nanorods loaded with celastrol localised to mitochondria in microglia, an important sire of action for celastrol. Results from this study suggest the potential of nanodelivery systems for CNS-targeted anti-inflammatory therapies.