Enhancement of oral bioavailability and anti-Parkinsonian efficacy of resveratrol through a nanocrystal formulation.

摘要: Abstract Resveratrol (RES), a non-flavonoid polyphenol extracted from wide variety of plants, exhibits neuroprotective activities against Parkinson's disease (PD). However, undesirable water solubility RES reduces its oral bioavailability and demonstrates low efficacy in blood brain, thus limiting application. In present study, nanocrystal formulation (RES-NCs) was developed to enhance delivery into brain for PD treatment. RES-NCs were fabricated with hydroxypropyl methylcellulose (HPMC) stabilizer via antisolvent precipitation approach. The obtained displayed the particle size 222.54 ± 1.66 nm, PDI 0.125 0.035, zeta potential −9.41 0.37 mV, rapid vitro dissolution rate. Molecular dynamics simulation HPMC revealed an interaction energy −68.09 kJ/mol binding −30.98 0.388 kJ/mol, indicating that spontaneous between two molecules is through van der Waals forces. conferred enhanced cellular uptake as well improved permeability relative pure RES. addition, able protect neurons cytotoxicity induced by MPP+. Meanwhile, exerted no significant toxic effects on zebrafish embryos larvae, did not influence their survival hatching rates. When orally administered rats, exhibited more favorable pharmacokinetics than RES, higher plasma concentrations. More importantly, MPTP-induced mice showed notable improvements behavior, attenuated dopamine deficiency, elevated levels metabolites after treatment RES-NCs. Furthermore, immunoblot analysis role may be at least partially mediated Akt/Gsk3β signaling pathway. Taken altogether, can serve modality PD, offering means improving accumulation.