Introduction: Alzheimer’s disease is a progressive neurodegenerative disorder where conventional oral delivery of donepezil hydrochloride is limited by poor bioavailability and restricted brain access due to the blood–brain barrier. This study aims to develop an alternative nanocarrier-based delivery system to enhance therapeutic efficacy. Method: Trestearin, phosphatidylcholine, and cholesterol formed a solid lipid core that was used to make emulsomes. TEM was used to characterize emulsomes, while FTIR spectroscopy was used for compatibility tests. The formulation was optimized using the 3-factor, 3-level Central Composite Design. Result: The optimized emulsome formulation demonstrated a stable formulation with a mean particle diameter of 124 ± 3.25 nm, an entrapment efficiency of 74 ± 0.67%, a PDI of 0.209 ± 0.03, with a zeta potential of -0.130 mV. In vitro release study demonstrated a consistent drugrelease pattern, with 84 ± 1.24% of the medication released during the investigation. Discussion: Based on insights from the thesis, emulsomes incorporating Nigella sativa oil show enhanced neuroprotective potential due to the antioxidant and anti-inflammatory actions of thymoquinone. The intranasal route further supports improved brain targeting by bypassing the blood–brain barrier. The consistency of particle size, strong entrapment efficiency, and sustained drug release align with the reported advantages of emulsome-based formulations discussed in the thesis, reinforcing their promise as an effective approach for Alzheimer's treatment. Conclusion: The central composite design optimization ensures a stable and effective delivery system for the donepezil hydrochloride-loaded emulsomes containing Nigella sativa oil with great potential for novel drug delivery in Alzheimer's disease.
Singh et al. (2026) studied this question.