From gut to brain: formulation and transporter-guided approaches to maximise rutin central nervous system delivery

Neurological disorders, including Alzheimer's and Parkinson's disease, are characterised by high morbidity and disability, representing a major global health challenge. A central obstacle in their treatment is the blood-brain barrier, a highly selective interface that limits drug delivery to the central nervous system. Rutin, a naturally occurring flavonoid, exhibits potent antioxidant, anti-inflammatory, and neuroprotective activities, yet its clinical utility remains constrained by poor solubility, low oral bioavailability, and restricted blood-brain barrier permeability. Recent advances in drug delivery and formulation science offer promising solutions. Nanoparticle encapsulation, peptide conjugation, intranasal delivery, and co-administration with absorption enhancers have been shown to improve rutin's solubility, metabolic stability, and central nervous system penetration in preclinical models. Mechanistic studies further reveal that rutin can modulate efflux transporters, regulate tight-junction proteins, and influence microglial activity and cellular metabolism, collectively contributing to enhanced neuroprotection. Experimental evidence highlights its potential to mitigate key neurodegenerative processes, particularly in Alzheimer's disease. This review synthesises current knowledge on rutin's pharmacological effects, limitations in bioavailability, and innovative strategies to improve blood-brain barrier penetration. By integrating mechanistic insights with advances in delivery technologies, this review underscores rutin's translational potential. Priority next steps include optimising delivery systems, establishing long-term safety, and conducting well-designed clinical trials to define efficacy and dosing.