口服纳米颗粒在胃肠道中的跨膜转运研究进展

Research Progress of Transmembrane Transport of Oral Nanoparticles in Gastrointestinal Tract

口服纳米颗粒逐渐成为改善生物药剂学分类系统(BCS)Ⅱ,Ⅲ及Ⅳ类药物口服生物利用度的潜在递药手段,其在胃肠道中的跨膜转运机制很大程度上取决于纳米颗粒的理化性质。采取合理的研究模型剖析口服纳米颗粒在胃肠道中的转运机制,揭示纳米颗粒的理化性质与转运机制之间的关系,将有助于指导设计具有更高转运效率的纳米载体,从而有效提高药物的口服生物利用度。笔者归纳了口服纳米颗粒的主要跨膜转运方式,对比分析了常用的细胞模型及其优缺点,并总结了纳米颗粒的理化性质如载体材料、粒径、形状、表面电荷、表面修饰等与跨膜转运机制之间的潜在联系,提出了基于在体肠吸收的纳米颗粒转运机制研究思路,以期为选择适合于不同纳米颗粒转运机制研究的细胞模型提供参考,为反馈调控纳米颗粒设计优化粒子转运性能进而提高药物口服生物利用度提供理论依据,并最终拓展口服纳米颗粒在新药研发中的应用。

Oral nanoparticles(NPs)has gradually become a approach to improve oral bioavailability of biopharmaceutics classification system(BCS)Ⅱ,Ⅲ,Ⅳ drugs,and the transmembrane transport mechanism in the gastrointestinal tract largely depends on physicochemical characteristics of NPs. It would be beneficial to design the NPs with high transport efficiency and effectively improve the oral bioavailability of drugs by adopting a reasonable research model to analyze the transmembrane mechanism of the oral NPs and exactly reveal the relationship between the physicochemical properties and the transport mechanism of NPs. This review focused on summarizing the transmembrane approaches of oral NPs, comparing the advantages and disadvantages of the common cell models,concluding the potential interaction between the physicochemical properties and transmembrane process of NPs,and proposing the research strategy of transport mechanism based on in situ intestinal perfusion,with the purpose of discovering a suitable research model for studying the transport mechanism of different NPs,providing a basis for regulating the transport performance of the NPs to improve the oral bioavailability,and expanding the application of oral NPs in the development of new drugs.