F127/SWCNTs对P-gp底物在大鼠小肠吸收影响的研究

目的：考察3种F127/SWCNTs载体系统的稳定性及对小肠P-糖蛋白（P-gp）药泵的抑制作用。方法：将F127/SWCNTs稀释至不同浓度后于4℃放置15 d，检测CNTs含量、粒径、Zeta电位等参数的变化；采用大鼠在体单向灌流模型进行肠吸收试验，以P-gp特异性底物罗丹明123（R-123）大鼠回肠段的吸收速率常数（K_a）和表观渗透系数（P_app）为考察指标，评价F127/SWCNTs对R-123肠吸收的影响。结果：储存稳定性和稀释稳定性均表明其中F127/SWCNT-COOH与F127/SWCNT-OH在15 d内4℃放置稳定性良好，无明显沉淀析出，粒径和含量稳定。3种F127/SWCNTs均可在不同程度增加R-123在回肠段的吸收，且具有浓度依赖性。结论：F127/SWCNTs可能通过抑制P-gp药泵作用改善P-gp底物药物的口服生物利用度，为药物特异性口服应用创造独特机会。

Effect of F127/SWCNTs on intestinal absorption of P-gp substrates in rats

OBJECTIVE To explore the stability and effect of three types of functionalized F127/SWCNTs on intestinal P-glycoprotein (P-gp).METHODS F127/SWCNTs was diluted to different concentrations with phosphate buffer saline (PBS) and maintained undisturbed for 15 days at 4 ℃. The stability of F127/SWCNTs suspension was determined by measuring the parameters of CNTs content, average particle size and Zeta potential. The rat single pass intestinal perfusion model in situ was employed for intestinal absorption test and rhodamine 123 (R-123) utilized as specific substrates of P-gp. Absorption rate constant (K_a) and apparent absorption coefficient (P_app) of R-123 in ileum were used for evaluating the effects of F127/SWCNTs on intestinal absorption of R-123.RESULTS The tests of storage stability and dilution stability all indicated that both F127/SWCNT-COOH and F127/SWCNT-OH maintained decent physical stability at 4 ℃. And CNT content and particle size showed little change. Three F127/SWCNTs significantly boosted K_a and P_app values of R-123 in ileum in different degrees. And such an effect was in a concentration dependent manner.CONCLUSION F127/SWCNTs may be capable of improving oral bioavailability of P-gp substrate by suppressing intestinal P-gp activity. F127/SWCNTs create unique opportunities for drug-specific oral delivery applications.