Modified self-assembled cannabidiol-albumin nanoparticles for enhanced brain delivery and neuroprotection in an Alzheimer's model

초록

Purpose Cannabidiol (CBD) exhibits potent antioxidant, anti-inflammatory, and neuroprotective properties; however, its therapeutic application in Alzheimer's disease (AD) is limited by poor aqueous solubility, instability, and restricted brain delivery. This study aimed to develop a nanoparticle-based delivery system to enhance CBD bioavailability and brain-associated therapeutic efficacy.Methods CBD-loaded human serum albumin nanoparticles (CBD-HSA-NPs) were prepared using a modified self-assembly technique. The physicochemical properties, encapsulation efficiency, and in vitro release behavior were characterized. Anti-amyloidogenic activity, reactive oxygen species (ROS) inhibition, and neuroprotective effects were evaluated in vitro. Cellular uptake was assessed in hCMEC/d3 cells using Cy5.5-loaded nanoparticles. In vivo therapeutic efficacy was investigated in an A beta(1)-(4)(2)-induced AD mouse model through behavioral, biochemical, and histological analyses.Results The optimized CBD-HSA-NPs exhibited a mean particle size of 197.2 +/- 1.1 nm, a polydispersity index of 0.283, and a zeta potential of - 27.8 +/- 0.8 mV, with high encapsulation efficiency (87.4 +/- 3.9%) and sustained drug release. Compared with free CBD, CBD-HSA-NPs significantly inhibited A beta aggregation, reduced ROS generation, and attenuated neuronal toxicity. In hCMEC/d3 cells, Cy5.5-loaded HSA-NPs demonstrated more than two-fold higher cellular uptake than free dye. In A beta(1)-(4)(2)-injected mice, treatment with CBD-HSA-NPs improved cognitive performance, reduced A beta burden, and decreased pro-inflammatory cytokines.Conclusion CBD-HSA-NPs represent a promising nanocarrier platform for enhancing CBD delivery and therapeutic efficacy in AD. The formulation demonstrates multifunctional activity, including anti-amyloidogenic, antioxidant, and anti-inflammatory effects, supporting its potential for brain-targeted therapy.

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