Enhanced oral bioavailability of morin administered in mixed micelle formulation with PluronicF127 and Tween80 in rats.
To overcome the low oral bioavailability of morin, a mixed micelle formulation with pharmaceutical excipients that facilitate solubilization and modulate P-glycoprotein (P-gp) was developed and evaluated in vitro and in vivo rats. Morin-loaded mixed micelle formulation with a morin-PluronicF127-Tween80 ratio of 1 : 10 : 0.02 (w/w/w) was prepared by a thin-film hydration method. The solubility, size distribution, drug encapsulation efficiency, and percent drug loading of the formulation were characterized. Subsequently, in vivo pharmacokinetic parameters of morin loaded in a PluronicF127 and Tween80 mixed-micelle formulation were investigated in rats. Absolute bioavailability of morin was dramatically increased by the oral administration of morin-loaded PluronicF127 and Tween80 mixed micelle from 0.4% to 11.2% without changing the systemic clearance and half-life. In Caco-2 cells, absorption permeability of morin from the novel formulation was increased 3.6-fold compared with that of morin alone. P-gp inhibition by cyclosporine A (CsA) increased absorptive permeability of morin 2.4-fold but decreased the efflux of morin by 52%, which was consistent with increased plasma concentration of morin in the pretreatment of CsA in rats. The morin formulation inhibited P-gp transport activity by 83.1% at 100 µM as morin concentration. Moreover, morin formulation increased paracellular permeability of Lucifer yellow by 1.6-1.8 fold. In conclusion, enhanced oral bioavailability of morin from morin-loaded PluronicF127 and Tween80 mixed micelle formulation can be attributed to increased intestinal permeation of morin, which was mediated at least by P-gp inhibition and enhanced paracellular route.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University.
Yeon Ah
YA
Choi
You Hyun
YH
Yoon
Kwangik
K
Choi
Mihwa
M
Kwon
Soo Hyeon
SH
Goo
Jin-Sun
JS
Cha
Min-Koo
MK
Choi
Hye Suk
HS
Lee
Im-Sook
IS
Song
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008823:Micelles; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry; D011136:Polysorbates / Q000008:administration & dosage* / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013552:Swine; D047309:Flavones
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D008823:Micelles; D020442:Poloxamer; D011136:Polysorbates; C008548:morin; D047309:Flavones