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

Abstract

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.

Keywords: 25mg/kg and 50mg/kg, CUR 25-I/R and CUR 50-I/R, respectively; AChE; BA; BBB; BCCAO; BSLN-I/R; Bioavailability; C-S; C-SLNs; CAT; Cerebral ischemia; Curcumin; Curcumin solubilized in Tween 80; EPM; GCI; GSH; I/R; ITL; LPO; MDA; MWM; Morris water maze; NO; Oxidative/nitosative stress; ROS; RTL; SLNs; SOD; Solid lipid nanoparticles; acetylcholinesterase; bilateral common carotid artery occlusion; bioavailability; blank SLNs; blood–brain-barrier; catalase activity; curcumin loaded solid lipid nanoparticles; curcumin suspended in 1% sodium carboxy methyl cellulose; cytosolic superoxide dismutase; elevalted plus maze; free curcumin; global cerebral ischemia; iNOS; inducible nitric oxide synthase; initial transfer latency; ischemic reperfusion; lipid peroxidation; malondialdehyde; nitric oxide; reactive oxygen species; reduced glutathione; retention transfer latency; solid lipid nanoparticles.