Oral Administration of Cannabidiol via Zirconium-Based Metal-Organic Frameworks: In Vivo Neuroprotective Effects in a C. elegans Alzheimer's Model

Cannabidiol (CBD) holds significant therapeutic promise for neurodegenerative pathologies. However, its clinical translation is severely restricted by poor aqueous solubility and susceptibility to degradation in the acidic gastric environment. To overcome these limitations, this study reports the encapsulation of CBD within NU-1000, a zirconium-based metal-organic framework (MOF) distinguished by exceptional acid stability and biocompatibility. The resulting composite, CBD@NU-1000, was optimized to attain a high drug loading capacity of approximately 50 wt% while maintaining the structural integrity of the MOF. Under simulated gastrointestinal fluids, NU-1000 effectively shielded CBD from gastric degradation and facilitated controlled release within the intestinal milieu. In vivo efficacy was assessed using a transgenic Caenorhabditis elegans model of Alzheimer's disease expressing human β-amyloid. Oral administration of CBD@NU-1000 significantly delayed the onset of β-amyloid-induced paralysis, demonstrating neuroprotective potency comparable to free CBD but with a superior, sustained therapeutic effect attributable to controlled release kinetics. Toxicological evaluations confirmed the biosafety of NU-1000 at therapeutic doses, evidencing efficient internalization and excretion without bioaccumulation risks. Consequently, this study establishes the potential of MOF-mediated encapsulation as a viable strategy to enhance the oral bioavailability and long-term efficacy of CBD in treating neurodegenerative disorders.