吐温-80对p-糖蛋白底物罗丹明123经肠粘膜透过性的影响

Effect of Tween-80 on the permeability of rhodamine 123,a P-gp substrate across rat intestinal membranes in vitro

目的观察低浓度吐温-80对肠粘膜P-gp的调控作用。方法使用体外扩散池评价罗丹明123(R123)经空肠,回肠和结肠粘膜的经时吸收方向和分泌方向的透过量和透过系数,并测定不同浓度吐温-80对R123和荧光素钠经肠粘膜透过性的影响。R123和荧光素钠在接受室中的浓度用荧光分光光度法测定。结果R123经肠道粘膜的透过性存在部位差,即以空肠、回肠和结肠的次序透过性依次减少。另一方面,R123经肠道分泌方向的透过性显著地高于其吸收方向的透过性。低浓度的吐温-80具有增加R123经吸收方向的透过性。但实验浓度的吐温-80对荧光素钠的肠道转运没有影响。结论低浓度的吐温-80可通过对P-gp功能的抑制而用于改善受P-gp介导药物的吸收,有望提高此类药物的口服生物利用度。

Objective To investigate the effect of Tween-80 in modulating rhodamine123 （R123） permeability across the intestinal membranes. Methods The permeability of R123 or fluorescein sodium （CF） across isolated rat intestinal membranes at the concentration of 5 μg/ml was evaluated using an in vitro diffusion chamber system, in the presence or absence of Tween-80 at different low concentrations. The concentration of R123 or CF in the receptor chamber was determined using fluorospectrophotometry. Results The intestinal membrane permeability of R123 gradually decreased from the jejunum to the ileum and then to the colon. The serosal-to-mucosal transport of R123 was much greater than its mucosal-to-serosal transport. In the presence of low concentrations of Tween-80, the absorptive transport of R123 was significantly increased while its secretory transport decreased depending on the concentration of Tween-80. However, Tween-80 at the experimental concentrations was found to obviously affect the CF transport across the intestinal membranes. Conclusion Low concentrations of Tween-80 may promote the absorption of P-gp-mediated drugs and therefore improve the oral bioavailability of these drugs.