Formulation Development and Evaluation of Intranasal Delivery of Imperatorin-Loaded Nanoemulgels for Attenuating Neurodegeneration in Rotenone-Induced Parkinson’s Disease

Research Article

Abstract

The therapeutic management of Parkinson’s disease therapy is challenging due to the restrictive nature of the blood-brain barrier and the systemic side effects associated with conventional oral medications. Imperatorin, a furanocoumarin bioactive, possesses potent antioxidant and neuroprotective properties, yet its clinical utility remains hampered by poor aqueous solubility and limited cerebral bioavailability. This work involves development of an Imperatorin-loaded nanoemulgel designed for direct nose-to-brain delivery to enhance therapeutic outcomes in a Parkinson’s-like rat model. Optimization through a Box-Behnken experimental design identified an ideal nanoemulsion comprising oleic acid, Tween 80, and Transcutol P, processed via high-energy ultrasonication. The optimized formulation exhibited a hydrodynamic droplet size of 71.05 nm, a polydispersity index of 0.202, and a high negative zeta potential of -60.0 mV, ensuring colloidal stability. Upon incorporation into a Carbopol 974P matrix, the resulting nanoemulgel showed shear-thinning rheological behavior and a sustained biphasic drug release profile, reaching 95.6% over 24 hours. In vivo evaluation in a rotenone-induced Parkinsonian model revealed that intranasal administration significantly restored motor coordination and locomotor activity in rotarod and open-field assessments. Biochemical analysis confirmed the mitigation of oxidative stress through reduced malondialdehyde levels and the restoration of superoxide dismutase activity, alongside a marked decrease in neuroinflammatory markers such as TNF-α. These results indicate that the Imperatorin nanoemulgel platform successfully bypasses systemic barriers, offering a direct and effective non-invasive strategy for neuroprotection in neurodegenerative disorders