This study aimed to develop a pH-responsive folic acid-grafted organic/inorganic hybrid na-nocomposite system for site-selective oral delivery of therapeutic antibodies.A folic acid-grafted amino-clay(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 mac-romolecules.A pH-responsive FA-AC-based nanocomplex containing IFX(EFA-AC-IFX)was also ob-tained 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-AC-IFX 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 effec-tive in alleviating the progression of ulcerative colitis,while oral IFX solution had no efficacy.These re-sults suggest that a pH-responsive FA-AC-based nanocomposite system can be a new platform for the site-selective oral delivery of therapeutic antibodies.

Sang Hoon Lee;Jae Geun Song;Hyo-Kyung Han

College of Pharmacy,Dongguk University-Seoul,Goyang 10326,South Korea

药学学报（英文版）

[1]Sang Hoon Lee;Jae Geun Song;Hyo-Kyung Han-.Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite system)[J].药学学报（英文版）,2022(11):4249-4261

nocomposite,nanocomplex,romolecules

Site,selective,oral,delivery,therapeutic,antibodies,inflamed,colon,folic,acid,grafted,inorganic,hybrid,nanocomposite,system,This,study,aimed,develop,responsive,amino,clay,AC,was,prepared,situ,gel,method,Then,drug,loaded,electrostatic,interaction,infliximab,IFX,model,antibody,coated,Eudragit,S100,EFA,exhibited,favorable,profiles,carrier,including,low,cytotoxicity,good,target,selectivity,capability,negatively,charged,mac,containing,also,ob,narrow,size,distribution,high,entrapment,efficiency,conformational,stability,entrapped,well,maintained,presence,proteolytic,enzymes,dependent,release,minimizing,premature,gastric,conditions,upper,intestine,Accordingly,administration,colitis,induced,mice,effec,alleviating,progression,ulcerative,while,solution,had,efficacy,These,sults,suggest,that,can,be,new,platform

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