Evaluation of the neuroprotective potential of optimized intranasal polydopamine nanoparticles in a lipopolysaccharide-induced rat model for Alzheimer’s disease management

Alzheimer's Disease (AD) and related dementias are on the rise globally, with forecasts suggesting that the case number will triple in the next three decades, particularly in Africa and the Middle East. This study aimed to prepare brain-targeted highly permeable intranasal polydopamine nanoparticles (PDA NPs) and to investigate their neuroprotective effect in AD. PDA NPs were fabricated via dopamine hydrochloride (DA HCl) polymerization using various safe and nontoxic surfactants to reduce particle size (PS) and enhance nasal penetration. A 4¹*2² full factorial design was employed. The optimized formulation was composed of 10 mg DA HCl and sodium taurocholate as a surfactant at pH 10. The optimized formulation was subjected to in vitro characterization: PS, polydispersity index (PDI), zeta potential (ZP), Transmission Electron Microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), in vitro cell cytotoxicity, and in vivo evaluation: in vivo tissue uptake using confocal laser scanning microscopy (CLSM) and investigation of neuroprotective effect in lipopolysaccharide-induced rat model. The optimized formulation produced minimal PS (111.3 nm), PDI (0.324), and maximum ZP (- 36.87 mV). PDA NPs showed high brain uptake and significant behavioral and biochemical results on rats as well as an elevation of dopamine expression and ameliorated neuron degeneration. PDA NPs exerted a neuroprotective effect in Alzheimer's disease through their anti-inflammatory and ACh/dopamine stimulation effects.