Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hy brid nanocomposite system  

作　　者：Sang Hoon Lee Jae Geun Song Hyo-Kyung Han 

机构地区：[1]College of Pharmacy,Dongguk University-Seoul,Goyang 10326,South Korea

出　　处：《Acta Pharmaceutica Sinica B》2022年第11期4249-4261,共13页药学学报（英文版）

基　　金：supported by National Research Foundation of Korea (NRF);South Korea grant funded by the Korea government(MSIT)(Nos. 2019R1A2C2004873 and 2018R1A5A2023127);the BK21 FOUR program through the National Research Foundation (NRF) funded by the Ministry of Education of Korea

摘　　要：This study aimed to develop a pH-responsive folic acid-grafted organic/inorganic hybrid nanocomposite system for site-selective oral delivery of therapeutic antibodies. A folic acid-grafted aminoclay(FA-AC) was prepared via an in situ sol-gel method. Then, a drug-loaded nanocomplex was prepared via the electrostatic interaction of FA-AC with infliximab(IFX), a model antibody, and coated with Eudragit? S100(EFA-AC-IFX). FA-AC exhibited favorable profiles as a drug carrier including low cytotoxicity, good target selectivity, and capability to form a nanocomplex with negatively charged macromolecules. A pH-responsive FA-AC-based nanocomplex containing IFX(EFA-AC-IFX) was also obtained in a narrow size distribution with high entrapment efficiency(>87%). The conformational stability of IFX entrapped in EFA-AC-IFX was well maintained in the presence of proteolytic enzymes. EFA-ACIFX exhibited pH-dependent drug release, minimizing premature drug release in gastric conditions and the upper intestine. Accordingly, oral administration of EFA-AC-IFX to colitis-induced mice was effective in alleviating the progression of ulcerative colitis, while oral IFX solution had no efficacy. These results suggest that a pH-responsive FA-AC-based nanocomposite system can be a new platform for the site-selective oral delivery of therapeutic antibodies.

关 键 词：INFLIXIMAB Aminoclay Colonic delivery:TNF-x Infammation Folate rceptor Anibody NANOCOMPOSITE 

分 类 号：R392-33[医药卫生—免疫学]