Regional intestinal absorption of FITC-dextran 4,400 with nanoparticles based on beta-sitosterol beta-D-glucoside in rats.
Nanoparticles (NP) are potential carriers for drug delivery to the targeted intestine. NP based on beta-sitosterol beta-D-glucoside (Sit-G) enhanced the colon-specific absorption of FITC-dextran 4,400 (FD-4), because the concentration-dependent increase of bioavailability appeared in only the colon. In a permeation study, the absorption enhancement in the colon was suppressed in the following conditions: (1) the addition of Sit-G NP to serosa; (2) a permeation study at 4 degrees C; (3) the addition of endocytosis inhibitor, cytochalasin B. NP based on sitosterol, the aglycon of Sit-G, did not increase the FD-4 colonic permeation. The addition of Sit-G NP to the mucosal side induced a decrease of transepithelial resistance (TEER), but this phenomenon was suppressed by an inhibitor of Na(+)-dependent specific glucose transporter, phrolidzin, which did not affect FD-4 permeation. These findings suggested that absorption enhancement by Sit-G NP may not be due to opening of a tight junction, but might be related to endocytosis via glucose residue of Sit-G.
Nakamura
Koji
K
Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
Takayama
Kozo
K
Nagai
Tsuneji
T
Maitani
Yoshie
Y
D000465:Algorithms; D000818:Animals; D003911:Dextrans / Q000493:pharmacokinetics*; D015194:Diffusion Chambers, Culture; D004705:Endocytosis; D005079:Excipients; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005614:Freeze Fracturing; D006027:Glycosides / Q000737:chemistry; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008863:Microspheres; D051381:Rats; D017208:Rats, Wistar; D012855:Sitosterols / Q000737:chemistry*; D013535:Suspensions
D003911:Dextrans; D005079:Excipients; D006027:Glycosides; D012855:Sitosterols; D013535:Suspensions; C015219:fluorescein isothiocyanate dextran; C025473:gamma-sitosterol; D016650:Fluorescein-5-isothiocyanate