Curcumin loaded solid lipid nanoparticles: An efficient formulation approach for cerebral ischemic reperfusion injury in rats

Scope: To evaluate curcumin loaded solid lipid nanoparticles (C-SLNs) in the experimental paradigm of cerebral ischemia (BCCAO model) in rats. Methods and results: Oral administration of free curcumin and C-SLNs (25 and 50 mg/kg) was started 5 days prior and continued for 3 days after BCCAO. Alleviation in behavioral, oxidative and nitrosative stress, acetylcholinesterase, mitochondrial enzyme complexes, and physiological parameters were assessed. Confirmation of effective brain delivery of C-SLNs (p.o) was done using biodistribution studies in mice and confocal microscopy of rat brain section. There was an improvement of 90% in cognition and 52% inhibition of acetylcholinesterase versus cerebral ischemic group (I/R). Neurological scoring improved by 79%. Levels of superoxide dismutase, catalase, glutathione, and mitochondrial complex enzyme activities were significantly increased, while lipid peroxidation, nitrite, and acetylcholinesterase levels decreased (p < 0.05) after C-SLNs administration. It is noteworthy to report the restoration of SOD, GSH, catalase, and mitochondrial complex enzyme levels equivalent to sham control values. Gamma-scintigraphic studies show 16.4 and 30 times improvement in brain bioavailability (AUC) upon oral and i.v administration of C-SLNs versus solubilized curcumin (C-S). Conclusions: Study indicates protective role of curcumin against cerebral ischemic insult; provided it is packaged suitably for improved brain delivery. (C) 2013 Elsevier B.V. All rights reserved.