RESVERATROL- AND PIPERINE-CO-LOADED NANOSTRUCTURED LIPID CARRIERS FOR INTRANASAL DELIVERY: DEVELOPMENT, CHARACTERIZATION, AND NEUROPROTECTIVE POTENTIAL IN PARKINSON’S DISEASE

Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss in the substantia nigra and debilitating motor and cognitive impairments. Conventional dopaminergic therapies often show limited brain bioavailability and significant side effects. Naturally occurring compounds such as resveratrol (RES) and piperine (PIP) exhibit potent neuroprotective, antioxidant, and anti-inflammatory activities but suffer from poor solubility and low oral bioavailability, restricting their therapeutic use.

Objective: The present study aimed to develop, characterize, and evaluate chitosan-coated nanostructured lipid carriers (NLCs) co-loaded with RES and PIP for intranasal delivery to achieve improved brain targeting and enhanced neuroprotective efficacy in PD.

Methods: RES- and PIP-loaded NLCs were prepared via high-pressure homogenization and ultrasonication using glyceryl monostearate and medium-chain triglycerides as lipid components. The formulations were optimized using solubility screening and central composite design. Physicochemical characterization included FTIR, dynamic light scattering, zeta potential, DSC, and TEM analyses. Entrapment efficiency, drug loading, pH, and in-vitro diffusion were determined.

Results: Optimized NLCs showed a mean particle size of 124.1 nm, zeta potential of +33.9 mV, PDI 0.329, and entrapment efficiency 88%. DSC and FTIR confirmed successful drug encapsulation and physicochemical compatibility. TEM revealed uniform spherical nanoparticles with smooth morphology. In-vitro studies demonstrated sustained and controlled drug release of ~95% over 24 h, with a final pH of 5.6 suitable for nasal administration.

Conclusion: The co-loaded RES-PIP NLCs present a stable, biocompatible, and effective intranasal nanocarrier system capable of bypassing the blood–brain barrier to deliver neuroprotective phytoconstituents directly to the brain.