title: Nanosuspension development of scutellarein as an active and rapid orally absorbed precursor of its BCS class IV glycoside scutellarin.
abstract: 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Miao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Fangrui
authors.initials: F
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Ai
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China.
authors.forename: Simon M Y
authors.initials: SMY
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao, China. Electronic address: yzheng@umac.mo.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D047310:Apigenin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D001711:Biotransformation; D002543:Cerebral Hemorrhage / Q000097:blood / Q000517:prevention & control; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D005965:Glucuronates / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D049329:Nanostructures; D036103:Nanotechnology; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D015027:Zebrafish; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D005079:Excipients; D005965:Glucuronates; D011355:Prodrugs; D047392:beta-Cyclodextrins; D020442:Poloxamer; C484876:scutellarin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D047310:Apigenin; C458179:scutellarein
keywords: Absorption; Cerebral hemorrhage; Metabolism; Nanotechnology; Oral drug delivery; Precursor; Scutellarin (SG); Solubility; Zebrafish