Differential distribution of intravenous curcumin formulations in the rat brain

Background: The neuropathic side-effects of trauma, stroke or therapeutic radiation of the brain for life-threatening neoplastic diseases are the result of damage to normal tissues resulting in defects in cognition and memory. Based upon published preclinical data of curcumin activity application of parenteral curcumin formulations may prove to be to be promising chemotherapy for disorders following neuropathic insults. Studies in in vitro and animal models suggest curcumin may be an effective remediative agent for brain damage. The initial steps in curcumin development for clinical applications to neuropathic disorders are formulating it for intravenous administration, determining the formulated product passes the blood-brain barrier and reaches therapeutic amounts in damaged areas in the brain with tolerable safety. Following intravenous administration of liposomal curcumin, polymeric nanocurcumin and polylactic glycolic acid co-polymer (PLGA)-curcumin in rats, these formulations were observed to cross the blood-brain barrier using a sensitive HPLC assay. All three formulations localized in specific sites in the brain without observable adverse events. One hour following intravenous injection of 5 mg/kg nanocurcumin, or 20 mg/kg PLGA-curcumin, or liposomal curcumin, up to 0.5% of the injected material localized in the brain stem, the striatum, and the hippocampus with varied accumulation and clearance rates. Conclusion: These data indicate that curcumin does localize in putative damaged brain tissues and suggest therapeutic trials be explored with all three formulations in animal models with pre- and post traumatic states.