Lipid nanocarrier of selegiline augmented anti-Parkinson’s effect via P-gp modulation using quercetin

Abstract

In the present study, SEL was loaded in a lipid nanocarrier (LNC) formulation with a P-gp pump inhibitor i.e., Quercetin (QUR) for improving the bioavailability of the SEL in the brain via the oral route. SEL-QUR LNC was formulated using modified emulsiosonication method and optimized using central composite rotatable design (CCRD) design. The results showed that optimized SEL-QUR LNC formulation was spherical with globule size, polydispersity index, entrapment efficiency and zeta potential within the range of 92.46–95.34 nm, 0.239–0.248, 88.94–91.26%, and −6.21 to −7.75 mV respectively. A 4-fold and 6-fold increase was observed in the permeation of SEL from SEL-QUR LNC across the gut sac in comparison with SEL-QUR and SEL suspensions respectively. CLSM images showed 2-fold deeper permeation of SEL across intestinal membrane demonstrating excellent in vivo prospect of the formulation. The behavioural studies including forced swimming, muscle coordination, locomotor activity, akinesia, and catalepsy were performed in the haloperidol-induced PD rats that demonstrated increased efficacy of the formulation in contrast to the SEL-QUR and SEL suspensions. These studies concluded that developed LNC formulation loaded SEL with P-gp inhibitor had the potential in improving bioavailability of SEL in the brain via oral route.