title: Hyperoside nanocrystals for HBV treatment: process optimization, in vitro and in vivo evaluation.
abstract: The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box-Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384 ± 21 nm and PDI of 0.172 ± 0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced Cmax (7.42 ± 0.73 versus 3.80 ± 0.66 mg/L) and AUC0 - t (193.61 ± 16.30 versus 91.92 ± 17.95 mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp.
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;
authors.forename: Baode
authors.initials: B
authors.lastname: Shen
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;|b Jiangxi University of Traditional Chinese Medicine , Nanchang , PR China ;
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;
authors.forename: Chengying
authors.initials: C
authors.lastname: Shen
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;
authors.forename: Fucheng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;
authors.forename: Pinghua
authors.initials: P
authors.lastname: Xu
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;|b Jiangxi University of Traditional Chinese Medicine , Nanchang , PR China ;
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: c Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA , School of Pharmacy, Fudan University , Shanghai , PR China ;
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: c Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA , School of Pharmacy, Fudan University , Shanghai , PR China ;
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: d 302 Military Hospital , Beijing , PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: d 302 Military Hospital , Beijing , PR China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Pharmacy , Air Force General Hospital, PLA , Beijing , PR China ;
authors.forename: Hailong
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D005612:Freeze Drying / Q000379:methods*; D006515:Hepatitis B virus / Q000737:chemistry / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012995:Solubility
chemical_list: C021304:hyperoside; D011794:Quercetin
keywords: Anti-HBV activity; bioavailability; high pressure homogenization; hyperoside; nanocrystals