scutellarein and Cerebral-Hemorrhage

This work addressed solubility and membrane permeability problems of Biopharmaceutics Classification System (BCS) Class IV glycoside scutellarin (SG) by developing a nanosuspension of its aglycone scutellarein (S) as a precursor. An S nanosuspension containing poloxamer 188 was prepared using antisolvent precipitation where hydroxypropyl-β-cyclodextrin was utilized as a lyophilizing protectant. Particle size and polydispersity index after redispersion were 342.6 ± 18.2 and 0.32 ± 0.06 nm, respectively. The dissolution rate of the S nanosuspension was superior compared with the physical mixture. No free S, but SG and SG's isomer were detected in plasma following oral delivery of SG or S, S nanosuspension or physical mixture of S. The Cmax values of SG after dosing with the S nanosuspension were 12.0, 8.0, and 4.5-fold higher than the SG, S, or physical mixture, respectively. The Tmax and mean residence time (MRTlast ) of SG after dosing with the S nanosuspension were significantly shorter than S and SG. Treatments with SG, S, or S nanosuspensions reduced the hemorrhage rate in a zebrafish model, but the S nanosuspension exhibited the strongest rescue effect. This study highlights a new strategy to circumvent BCS Class IV flavonoid glycosides using a formulation of their aglycone as a precursor to accelerate oral absorption and improve bioactivity.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Animals; Apigenin; beta-Cyclodextrins; Biological Availability; Biotransformation; Cerebral Hemorrhage; Chemistry, Pharmaceutical; Disease Models, Animal; Excipients; Freeze Drying; Glucuronates; Nanostructures; Nanotechnology; Particle Size; Poloxamer; Prodrugs; Rats, Sprague-Dawley; Solubility; Technology, Pharmaceutical; Zebrafish