In vivo evaluation of anionic thiolated polymers as oral delivery systems for efflux pump inhibition.

摘要: Abstract Recently, the cationic polymer thiolated chitosan has been reported to modulate drug absorption by inhibition of intestinal efflux pumps. The objective this study was evaluate in vitro and vivo whether anionic biopolymers also show an pump inhibitory effect order improve transcellular uptake. Therefore, three thiomers have synthesized due covalent attachment cysteine various backbones: pectin–cysteine (pect–cys), carboxymethylcellulose-cysteine (CMC–cys) alginate–cysteine (alg–cys). In vitro, permeation enhancing properties these their corresponding unmodified polymers evaluated on rat small intestine Ussing-type chambers, using sulforhodamine 101 (SR-101) as MRP2 model substrate. comparison buffer only, SR-101 transport presence pect–cys, CMC–cys alg–cys improved 1.5-fold, 1.8-fold 3.0-fold, respectively. Due comparatively best performance alginate, it chosen for studies: a solution containing 4% (w/v) led AUC 0≥12 109 ng ml −1  h rats representing 3.8-fold improvement solution. Unmodified alginate factor 1.9. These findings suggest promising auxiliary agent drugs being substrates, since oral bioavailability substrate could be significantly improved.