Comparative pharmacodynamic study delineating the efficacy of amantadine loaded nano-emulsified organogel via intranasal versus transdermal route in rotenone-induced Parkinson's disease rat model

Owing to the dysphagia and gastroparesis in patients concomitant with Parkinson's disease (PD), oral amantadine (AMT) medications are susceptible to poor bioavailability and clinical outcomes. A self-given delivery system controlling the release of AMT is sought to attain high patient compliance and enhanced therapeutic effect. This work focuses on the synthesis of a new potent low-molecular weight organogelator for the formulation of AMT nano-emulsified organogel (AMT-NEO). Among the gelators, the N-palmitoyl l-serine methyl ester (PSM) was selected for its highest gelation power and lowest critical gelation concentration. The D-optimal design was adopted for optimization of formulation variables; A: PSM amount, B: oil amount, and C: oil type. Evaluation of the particle size, zeta potential, polydispersity index, and AMT release was performed for all the formulations. The desirability function of the optimized formula was 0.949. The optimized formula possessed small particle size (162.58 nm), low polydispersity index (0.373), high zeta potential (−22.24 mV) and controlled the AMT release over 12h. A comparative pharmacodynamic study of the intranasal versus the transdermal administration of the optimized AMT-NEO to rats with rotenone-induced PD was performed. The results demonstrated the superiority of the nasal route to neutralize the deleterious effect of rotenone on motor behaviour and the measured biochemical parameters without affecting the histopathological morphology of nasal vestibules or skin layers. Therefore, the intranasal AMT-NEO might offer a shifted paradigm for the controlled release of such polar drug for the management of PD. This will be highly important especially for PD patients suffering from dysphagia.