转运体介导的纳米递送系统促进药物口服吸收的研究进展

Transporter-mediated Nano-delivery System in Promoting Oral Absorption of Drugs:A Review

口服给药是一种最为便利的给药方式,但由于肠道屏障的存在,药物的口服生物利用度普遍较低,尤其对于水溶性低、渗透性差和大分子药物更为明显。几十年来,研究者们已证明纳米递送系统是解决这一问题最有效的策略之一,但纳米递送系统对药物的口服生物利用度提高有限。为此,研究者们提出利用转运体介导的纳米递送系统来促进药物的口服吸收。摄取营养物质(如葡萄糖、寡肽、胆汁酸等)的转运体在肠道上高度表达,是口服递药系统的优良靶点,将其底物修饰在纳米递送系统上,通过转运体靶向的作用可以使负载药物更高效地跨过肠道屏障进入体循环。目前越来越多的证据支持转运体在口服递药系统领域的潜力,现将肠道转运体介导纳米递送系统促进药物口服吸收的研究进行梳理,包括肠道上转运体的分布、转运体底物修饰的3种策略,以及不同类型转运体的转运特性及其介导纳米递送系统促进药物口服吸收或治疗疾病的效果,以期为开发肠道靶向纳米递送系统提供重要的理论参考。

Oral administration is the most convenient way of drug delivery,but due to the existence of intestinal barrier,the oral bioavailability of drugs is generally low,especially for drugs with low water solubility,poor permeability and macromolecules.For decades,researchers have demonstrated that nanodelivery system is one of the most effective strategies to solve this problem,but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs.Therefore,researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs.The intestinal tract were highly expressed as a transporter for ingesting various nutrients(such as glucose,oligopeptides and bile acids),which was an excellent target of oral drug delivery system.Its substrate were modified on the nano-delivery system,and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters.At present,more and more evidences supported the potential of transporters in the field of oral drug delivery system.Therefore,this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs,including the distribution of intestinal transporters,three strategies of transporter substrate modification,the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases,with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.