Nano-ropinirole for the management of Parkinsonism: blood-brain pharmacokinetics and carrier localization

Abstract

Aim: The aim of this study was to investigate the brain targeting potential of chitosan-coated oil in water nanoemulsions (CSNE(ROP)) delivered intranasally in haloperidol-induced Parkinson's disease rat models.

Methods: Chitosan-coated nanoemulsion (CSNE(ROP)) was developed through aqueous titration followed by a high pressure homogenization method.

Results: Gamma-scintigraphy study showed a significantly high mucoadhesive potential of CSNE(ROP) and least for conventional and homogenized formulations. Confocal study showed deep localization of formulations in the brain confirming the permeation potential of CSNE(ROP). Pharmacokinetic results of CSNE(ROP) in Wistar rat brain and plasma showed a significantly high (p** < 0.005) AUC0→24 and amplified Cmax over i.v treatment group. Neurobehavioral activity (rotarod and swim tests) and biochemical parameters (glutathion, TBARS and SOD) corroborated well with the pharmacokinetic results. The order of dopamine recovery in haloperidol-induced Wistar rats was found to be (i.n)CSNEROP group>(i.n)SolnROP group>(i.v)SolnROP group>haloperidol group.

Conclusions: Finally, the investigation demonstrated that intranasal delivery of mucoadhesive nanocarrier might play as a potential candidate in the management of Parkinson's disease and related brain disorders.

Keywords: Confocal microscopy; Parkinsonism; brain targeting; intranasal drug delivery; nano-ropinirole.