Poly (ethylene glycol)-block-poly (D, L-lactide) (PEG-PLA) micelles for brain delivery of baicalein through nasal route for potential treatment of neurodegenerative diseases due to oxidative stress and inflammation: An in vitro and in vivo study.

The application of baicalein (BE) in central nervous system (CNS) neurodegenerative diseases is hampered by its poor solubility and low oral bioavailability despite its neuroprotective effects. In this study, BE was encapsulated into poly (ethylene glycol)-block-poly (D, L-lactide) micelles (BE-MC) and administrated through nasal inhalation to enhance its brain distribution. BE-MC showed comparable in-vitro antioxidant activity to BE solution. Cytotoxicity study illustrated BE-MC could reduce BE's toxicity in SH-SY5Y cells and BV-2 cells. BE solution at concentration higher than 5 µM caused significant BV-2 cells' death after stimulation of LPS while BE-MC were non-toxic to cells at concentrations up to 50 µM. BE solution at 5 µM had no anti-inflammatory effects in BV-2 cells while BE-MC could reduce the inflammatory factor TNF-α at 5 µM and IL-6 at 20 µM significantly. Pharmacokinetic studies in C57BL/6 mice showed the absolute AUC values of BE in plasma and brain of BE-MC through nasal inhalation group were 5.09-fold and 1.50-fold higher than that of BE coarse powder through oral administration group at the same dose. Thus, our study indicated BE-MC administered nasally could be useful for treatment of CNS neurodegenerative diseases due to oxidative stress and inflammation.

Pubmed ID: 33069896