摘要Paeoniflorin(PA)is an anti-Parkinson Chinese medicine with inferior bioavailability and difficulty in delivery to the brain.This research is to develop an efficacious PA nanocrystal formulation(PA-NCs)that is suitable for intranasal administration to treat Parkinson's disease(PD).PA-NCs were fabricated through an antisolvent precipitation method using TPGS as the stabilizer.The rod-shaped PA-NCs had particle size of 139.6±1.3 nm and zeta potential of-23.2±0.529 mV.A molecular dynamics simulation indicated that van der Waals forces are the primary drivers of interactions between PA and TPGS.In the ex vivo nasal mucosa permeation assay,the cumulative drug release at 24h was 87.14％±5.34％,which was significantly higher than that of free PA.PA-NCs exhibited substantially improved cellular uptake as well as permeability on Calu-3 cells as compared to PA alone.FRET imaging analysis demonstrated that intact NCs could be internalized into Calu-3 cells.Moreover,PA-NCs conferred desirable protective effect against MPP+-induced SH-SY5Y cellular damage.Pharmacokinetic studies revealed a higher PA concentration in the brain following intranasal delivery of PA-NCs.In summary,the intranasal administration of PA-NCs is a promising treatment strategy for PD.