Nose-to-brain lipid nanocarriers: An active transportation across BBB in migraine management

Abstract

The present study focused on the development and evaluation of nanotechnology-based carrier systems of solid lipid nanoparticles (SLNs) to enhance the permeation and bioavailability of zolmitriptan across blood-brain-barrier (BBB). SLNs are the emerging field of nanotechnology with numerous applications like cosmetics and pharmaceutical research. Zolmitriptan-loaded SLNs were prepared by high-pressure homogenization method for targeted drug delivery to the brain. The SLNs were found to be round in shape with particle size ranging from 110 to 200 nm and zeta potential upto − 24.83 ± 3.03 mV which indicates good colloidal stability. The maximum entrapment efficiency of zolmitriptan in SLNs was found to be 84.17 ± 12.24%. The in-vitro drug release and ex-vivo release studies exhibited 95.85 ± 2.44% and 82.06 ± 2.94% drug release, respectively for 24 h. In-vivo studies was performed on male Wistar rats wherein the concentration of zolmitriptan was estimated in cerebrospinal fluid by LC-MS method. The selected formulation incorporated with SLNs showed significant enhancement in pharmacokinetic parameters like AUC (37.05 ± 2.45 ng/mL), Cmax (42.08 ± 1.32 ng/mL), Tmax (30 min), and t1/2 (1.28 h). Zolmitriptan-loaded SLNs via intranasal administration offers a novel approach to effectively circumvent first-pass hepatic metabolism than conventional oral route with 4-fold alleviation in permeation and 2-fold improvement in bioavailability.