RRC ID 63260
著者 Seki T, Hamada A, Egawa Y, Yamaki T, Uchida M, Natsume H, Kimura S, Ueda H.
タイトル Evaluation of the effects of absorption enhancers on Caco-2 cell monolayers by using a pore permeation model involving two different sizes.
ジャーナル Biol Pharm Bull
Abstract We applied a parallel pore permeation model based on the Renkin molecular sieving function by using two different-sized pathways to analyze the permeation-enhancing effects of poly-L-arginine (PLA) or a mixed system of spermine (SPM) and sodium taurocholate (STC). Four paracellular markers were simultaneously applied to Caco-2 cell monolayers, and a set of apparent permeability coefficient (P) values was used to obtain membrane parameters. For PLA treatment, the pore occupancy/length ratio (ε/L) of the large pathways increased while the pore radius (R) did not, suggesting that the number of large pathways for the relatively large hydrophilic molecules in the monolayers could be increased by the addition of PLA. In contrast, application of the mixed system comprising SPM and STC significantly increased not only the R of the large pathways but also ε/L of the small pathways. Such changes in membrane parameters could be related to the enhancing mechanism of these compounds. The simulation curves for molecular weight (MW)-P calculated from the membrane parameters could be used to predict the P of drugs with different MWs.
巻・号 36(11)
ページ 1862-6
公開日 2013-1-1
DOI 10.1248/bpb.b13-00471
PII DN/JST.JSTAGE/bpb/b13-00471
PMID 24189430
MeSH Absorption / drug effects Caco-2 Cells Erythritol / metabolism Humans Inulin / metabolism Isomaltose / metabolism Peptides / pharmacology* Permeability / drug effects Porosity Spermine / pharmacology* Taurocholic Acid / pharmacology* Xylitol / metabolism
IF 1.863
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)