The study investigates the formulation and characterization of polymeric lipid hybrid nanoparticles (PLHNs) for targeted delivery of Rivastigmine and Convolvulus pluricaulis (C. pluricaulis, Shankhpushpi) extract to the brain. Employing a modified film hydration technique, PLHNs were optimized by adjusting lipid-to-polymer ratios, achieving nanoparticles with optimal size, zeta potential, and entrapment efficiency. The resulting nanoparticles, with sizes between approximately 150–225 nm, exhibited excellent physical stability and encapsulation efficiencies. Characterization through transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed their spherical and smooth morphology. Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) analyses showed no significant interactions between the drug, polymer, and plant extract, ensuring formulation stability. In vitro release studies demonstrated a controlled and sustained drug release, with the optimal formulation showing substantial release over 24 hours. The novel object recognition (NOR) test indicated enhanced cognitive function in animals treated with the optimal formulation, suggesting effective brain targeting and neuroprotective activity. Biochemical analyses supported these findings, revealing significant improvements in antioxidant enzyme levels and reductions in oxidative stress markers in treated animals. This study underscores the potential of PLHNs to enhance the delivery of neuroprotective agents, offering a promising strategy for treating neurodegenerative diseases.
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