Development of donepezil hydrochloride-loaded PLGA-based nanoparticles for Alzheimer’s disease treatment

In recent years, nanoparticle (NP) systems have demonstrated significant promise in pharmaceutical applications. This study focused on the development of donepezil hydrochloride-loaded PLGA-NPs, prepared using the 'Double Emulsion Solvent Evaporation' method. The impact of varying concentrations of polyvinyl alcohol-(PVA) in the aqueous phase and sonication time on NP characteristics was comprehensively examined. Results showed that increasing PVA concentration and sonication time resulted in a reduction in NP size, with an optimal formulation (I-DNP) achieving a particle size of 136.37 nm ± 0.93 and a PDI of 0.122 ± 0.011, indicating uniformity. The zeta potential was measured at - 24.17mV ± 1.21, confirming the electrostatic stability of the formulation, essential for long-term stability. Trehalose was incorporated to enhance stability, and gastrointestinal stability testing revealed that I-DNP degraded faster in acidic environments. The encapsulation efficiency reached 69.22 ± 4.84%, suggesting effective drug loading, and release studies exhibited a sustained release profile, with a Fickian and non-Fickian release mechanism. DSC, FT-IR, and ¹H-NMR analyses confirmed the encapsulation and structural integrity of the formulation. In biological activity studies, I-DNP exhibited potent anti-AChE and anti-BuChE activities, with Chorioallantoic Membrane (CAM) assays showing significant inhibition of angiogenesis. These findings highlight the potential of I-DNP as a promising therapeutic strategy for Alzheimer's disease, demonstrating its ability to enhance drug stability, controlled release, and potential blood-brain barrier (BBB) penetration. Future studies will focus on long-term stability testing and in vivo Alzheimer's models to further validate its clinical applicability. This research contributes to the advancement of nanoparticle-based drug delivery systems for neurodegenerative diseases, paving the way for innovative therapeutic approaches.