Intranasal delivery of DPSC-derived small extracellular vesicles-encased phloroglucinol attenuates non-motor and motor deficits and promotes neurogenesis in an in vivo rat model of Parkinson’s disease

• Intranasal delivery of sEV-encased phloroglucinol (sEV-Phl) significantly reduces oxidative stress and lipid peroxidation in a chronic MPTP rat model of Parkinson’s disease. • sEV-Phl treatment markedly improves both motor and non-motor behavioral deficits in PD rats, suggesting potential for comprehensive symptomatic relief. • The therapy promotes neurogenesis, as evidenced by increased markers (Ki67, BrdU, FOXA2), indicating regenerative potential in the diseased brain. • DPSC-derived sEVs serve as effective nanocarriers for targeted drug delivery across the blood-brain barrier via intranasal administration, enhancing the clinical applicability of phloroglucinol.