The prevalence of Alzheimer's disease (AD) in developed and developing nations is increasing day by day. The monotherapy doesn't fit best for AD due to chronic treatment. This work aimed to prepare the liposomes coloaded with Donepezil and pine oil intended for adjuvant effect. Pine oil was selected due to its amyloid disaggregation and AChE inhibition property. The thin film hydration method with sonication was selected to formulate ultra-small-sized unilamellar vesicles. Apart from this formulated vesicle were subject to particle size, morphological, release, nasal ciliotoxicity and cellular uptake studies. The PDI, particle size, and zeta potential of the final egg lecithin-based liposome were found to be 0.19, 129 nm, and -27.5 mV, respectively, stable at 4° and 25°C. SEM microscopy of oil-loaded liposomes exhibits a crystalline cubic shape and is compared with alone drug-loaded liposomes that are spherical. AChE inhibition activity was found to be higher in combination when compared with others. The prepared liposomes were safe when studied for nasal ciliotoxicity studies and rapid uptake by C6 cells with complete internalization. This study demonstrated the development and potential of the vesicular system that carries valuable characteristics and overcomes patient compliance concerns that prove to be novel therapeutics for managing AD.

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