Solid lipid nanoparticle: A potent vehicle of the kaempferol for brain delivery through the blood-brain barrier in the focal cerebral ischemic rat.

ABSTRACT

Kaempferol is major flavonoid present in Convolvulus pluricaulis. This phytochemical protects the brain against oxidative stress, neuro-inflammation, neurotoxicity, neurodegeneration and cerebral ischemia induced neuronal destruction. Kaempferol is poorly water soluble. Our study proved that solid lipid nanoparticles (SLNs) were efficient carrier of kaempferol through blood-brain barrier (BBB). Kaempferol was incorporated into SLNs prepared from stearic acid with polysorbate 80 by the process of ultrasonication. Mean particle size and zeta potential of kaempferol loaded solid lipid nanoparticles (K-SLNs) were 451.2 nm and -15.0 mV. Atomic force microscopy showed that K-SLNs were spherical in shape. Fourier transformed infrared microscopy (FTIR) showed that both stearic acid and kaempferol were present in K-SLNs. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed that the matrices of K-SLNs were in untidy crystalline state. Entraptment efficiency of K-SLNs was 84.92%. In-vitro drug release percentage was 93.24%. Kaempferol loaded solid lipid nanoparticles (K-SLNs) showed controlled release profile. In-vitro uptake study showed significant efficiency of K-SLNs to cross blood-brain barrier (BBB). After oral administration into the focal cerebral ischemic rat, accumulation of fluorescent labeled K-SLNs was observed in the brain cortex which confirmed its penetrability into the brain. It significantly decreased the neurological deficit, infarct volume and level of reactive oxygen species (ROS) and decreased the level of pro-inflammatory mediators like NF-κB and p-STAT3. Damaged neurons and brain texture were improved. This study indicated increased bioavailability of kaempferol into the brain tissue through SLNs formulation.