CCRD based development of bromocriptine and glutathione nanoemulsion tailored ultrasonically for the combined anti-parkinson effect

Abstract

Bromocriptine Mesylate (BRM) acts as a dopamine receptor agonist along with antioxidant effect and is utilized in the treatment of Parkinson’s disease (PD). Glutathione (GSH) is a thiol- reducing agent having antioxidant properties in the brain. Replenishment of GSH inside the brain can play a major role in the management of PD. Both BRM and GSH suffer from low oral bioavailability and poor absorption. The objective of the present study was to develop BRM and GSH loaded nanoemulsion for the combined and synergistic effect delivered through the intranasal route for the better and effective management of PD. After extensive screening experiments, Capmul PG-8 NF was selected as oil, polyethylene glycol (PEG) 400 as a surfactant and propylene glycol as co-surfactant. Ultrasonication technique was employed for the fabrication of nanoemulsion. Central composite rotatable design (CCRD) was used to obtain the best formulation by optimization. Oil (%), Smix (%), and sonication time (second) were chosen as independent variables for the optimization. Particle size, PDI, zeta potential, % transmittance, pH, refractive index, viscosity and conductivity of the optimized nanoemulsion were found to be 80.71 ± 2.75 nm, 0.217 ± 0.009, −12.60 ± 0.10 mV, 96.00 ± 3.05 %, 6.48 ± 0.28, 1.36 ± 0.03, 30.12 ± 0.10 mPas and 214.28 ± 2.79 μS/cm respectively. Surface morphology demonstrated that nanoemulsion possessed spherical and globular nature of the particle which showed 3.4 times and 1.5 times enhancement in drug permeation in the case of BRM and GSH respectively as compared to suspension. MTT assay done on neuro-2a cell lines revealed that nanoemulsion was safe for intranasal delivery. Behavioural studies were carried out to prove the efficacy of optimized nanoemulsion in PD using forced swimming test, locomotor activity test, catalepsy test, rota-rod test, and akinesia test in Wistar rats. The outcomes of the behavioural studies revealed that BRM and GSH loaded nanoemulsion treatment showed significant improvement in behavioural activities of PD (haloperidol-induced) rats after intranasal administration. This study concluded that BRM and GSH loaded nanoemulsion could be promising for the combined and synergistic anti-parkinson effect for the effective management of PD.