脂质纳米载体用于口服递送蛋白多肽药物的研究进展  

Research Progress of Lipid Nanocarriers for Oral Delivery of Protein and Peptide Drugs

作　　者：欧阳俊芳 张永杰 陈西敬 OUYANG Junfang;ZHANG Yongjie;CHEN Xijing(School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198)

机构地区：[1]中国药科大学基础医学与临床药学学院,江苏南京211198

出　　处：《中国医药工业杂志》2022年第9期1240-1250,共11页Chinese Journal of Pharmaceuticals

基　　金：江苏省自然科学基金项目(BK20190557)。

摘　　要：蛋白多肽药物具有良好的特异性和生物相容性,治疗效果较好。由于口服给药途径的患者顺应性和安全性更佳,蛋白多肽药物的口服递送已成为当前材料学与药剂学领域的研究热点之一。然而,口服生物大分子药物在胃肠道的稳定性及吸收程度却非常受限。脂质纳米载体能通过化学修饰、疏水离子配对等多种方式有效包载亲脂或亲水性蛋白多肽药物,同时经表面修饰后的脂质纳米载体能克服口服吸收的众多生理屏障,继而促进药物在混合胶束中溶解,增强淋巴摄取,因此具有良好生物相容性和体内稳定性。本研究综述了脂质纳米载体对蛋白多肽药物的包载方式及其克服生理屏障的相应机制,介绍了其提高蛋白多肽药物口服生物利用度的重要特性和最新研究进展,并展望了其潜在应用及发展前景。Protein and peptide drugs(PPDs) have good specificity,biocompatibility and good therapeutic effects.Due to the better patient compliance and safety of oral administration route,the oral delivery of PPDs has become one of the current research hotspots in the field of materials science and pharmaceuticals.However,the stability and absorption of oral biomacromolecules in the gastrointestinal tract are restricted.Lipid nanocarriers can effectively encapsulate lipophilic or hydrophilic PPDs through chemical modification,hydrophobic ion pairing and other methods.At the same time,the surface modification of lipid nanocarriers can overcome many physiological barriers of the oral absorption,which in turn promote the dissolution of PPDs in mixed micelles and strengthen lymphatic uptake.Therefore,it has good biocompatibility and high in vivo stability.In this paper,the encapsulation methods of lipid nanocarriers for PPDs and the corresponding mechanisms of overcoming physiological barriers are reviewed,and the important properties and latest research progress of lipid nanocarriers to improve the oral bioavailability of PPDs are introduced,the potential application and development prospects are further prospected as well.

关 键 词：脂质纳米载体 蛋白 多肽 口服给药 吸收屏障 生物利用度 

分 类 号：R944.9[医药卫生—药剂学]