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) AUC_0→24 and amplified C_max 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.nCSNE_ROP group>^i.nSoln_ROP group>^i.vSoln_ROP 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:

• brain targeting
• Confocal microscopy
• intranasal drug delivery
• nano-ropinirole
• Parkinsonism

Acknowledgements

The authors are thankful to Council for Scientific and Industrial Research (CSIR), New Delhi for CSIR-SRF which supported this study. The help provided by SAIF, AIIMS, New Delhi for using transmission electron microscopy facility for surface morphology cannot be left unacknowledged.

Financial & competing interests disclosure

Wockhardt Pharmaceuticals (Aurangabad, India), Gattefosse (Saint Priest, Cedex France) and Nikko Chemical Ltd (Japan) provided ROP, transcutol and sefsol 218, respectively. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Mucoadhesive and thermodynamically stable nano-ropinirole was developed by aqueous titration technique.

• The penetrating potential of nano-ropinirole was determined by confocal microscopy.

• Surface coating of nano-ropinirole with cationic charged mucoadhesive carbohydrate was authenticated by scintigraphy.

• A novel technique for simultaneous in vitro, ex vivo, and in vivo study.

• UHPLC-MS/MS-Q-TOF-based pharmacokinetic study and brain targeting potential.

• Formulation effectiveness interns of pharmacodynamic study were conducted in a haloperidol-induced rat model.

• Study showed intranasal drug delivery system could be a promising route for brain targeting.

Notes