Proof of concept studies to confirm the delivery of curcumin loaded solid lipid nanoparticles (C-SLNs) to brain

Abstract

Having achieved a significant bioavailability of curcumin by its incorporation into SLNs (C-SLNs) during pharmacokinetic (32-155 times) and pharmacodynamic (3-4 times) studies, our intent was to proof their targeting to brain. Hence, fluorescent/confocal microscopy, biodistribution and gamma scintigraphy techniques were explored to observe the presence of C-SLNs in the brain. 1h post p.o administration of C-SLNs/free curcumin (C-S) to rats, blood was withdrawn, following which the animals were sacrificed and their harvested brains were frozen at -80°C. The obtained plasma and brain cryosections were observed for fluorescence under fluorescent/confocal microscope. Biodistribution study was performed using (99m)Tc-labeled C-SLNs and C-S in Balb/c mice after p.o. and i.v. administration and % radioactivity/g organ was recorded. Subsequent to this gamma scintigraphs of the New Zealand rabbits following similar treatments were performed. Presence of yellow fluorescent particles in plasma and brain indicated effective delivery of C-SLNs across the gut wall and the BBB. (Blood)AUCoral value for C-SLNs was 8.135 times greater than that for C-S, confirming a prolonged circulation of former. The ratio of blood AUCi.v. C-SLN/C-S in blood is ≤1 while the ratio in brain promisingly indicates 30 times higher preferential distribution of C-SLNs into brain confirming their direct delivery.