低浓度N-三甲基壳聚糖对依托泊苷经肠黏膜透过性的影响

Modulation effects of low-concentration N-trimethyl chitosan chloride on the permeability of etoposide across different intestinal membranes

背景:N-三甲基壳聚糖作为透皮吸收促进剂,可以影响口服药物在体内经肠黏膜的透过性。目的:考察低浓度N-三甲基壳聚糖对依托泊苷经肠黏膜透过性的影响。方法:使用体外扩散池法评价依托泊苷经肠黏膜经时吸收方向和分泌方向的透过量和透过系数,并测定10%N-三甲基壳聚糖对依托泊苷经肠黏膜透过性的影响。依托泊苷在接受室中的浓度用高效液相色谱法测定。结果与结论:10%N-三甲基壳聚糖具有增加依托泊苷经吸收方向的透过性,减少经分泌方向的透过性。说明低浓度的N-三甲基壳聚糖可用于改善受P-糖蛋白介导药物的吸收,有望提高此类药物的口服生物利用度。

BACKGROUND： N-trimethyl chitosan as a transdermal enhancer can affect the permeability of oral drugs through the intestinal mucosa. OBJECTIVE： To investigate the modulation effects of N-trimethyl chitosan chloride on the permeability of etoposide across different intestinal membranes. METHODS： The permeability of etoposide via rat intestinal membranes was evaluated by an in vitro diffusion chamber system after the membranes were isolated from the intestine in rats with or without the co-administration of 10% N-trimethyl chitosan chloride. The concentration of etoposide in the receptor was determined by the high performance liquid chromatography. RESULTS AND CONCLUSION： With co-administration of N-trimethyl chitosan chloride at a low concentration, the absorptive directed transport of etoposide was significantly increased while its secretory directed transport was decreased. It might be possible to improve the absorption of P-glycoprotein mediated drugs by co-administration of N-trimethyl chitosan chloride at a low concentration, therefore to improve the oral bioavailability of these drugs.