Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite system
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221138352200274X |
| _version_ | 1811334317196967936 |
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| author | Sang Hoon Lee Jae Geun Song Hyo-Kyung Han |
| author_facet | Sang Hoon Lee Jae Geun Song Hyo-Kyung Han |
| author_sort | Sang Hoon Lee |
| collection | DOAJ |
| description | 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-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 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. |
| first_indexed | 2024-04-13T17:06:02Z |
| format | Article |
| id | doaj.art-6537108c8a2349ab87e5e5cf635b9fcd |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-13T17:06:02Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-6537108c8a2349ab87e5e5cf635b9fcd2022-12-22T02:38:27ZengElsevierActa Pharmaceutica Sinica B2211-38352022-11-01121142494261Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite systemSang Hoon Lee0Jae Geun Song1Hyo-Kyung Han2College of Pharmacy, Dongguk University-Seoul, Goyang 10326, South KoreaCollege of Pharmacy, Dongguk University-Seoul, Goyang 10326, South KoreaCorresponding author. Tel.: +82 31 9615217.; College of Pharmacy, Dongguk University-Seoul, Goyang 10326, South KoreaThis 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-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 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.http://www.sciencedirect.com/science/article/pii/S221138352200274XInfliximabAminoclayColonic deliveryTNF-αInflammationFolate receptor |
| spellingShingle | 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 Acta Pharmaceutica Sinica B Infliximab Aminoclay Colonic delivery TNF-α Inflammation Folate receptor |
| title | Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite system |
| title_full | Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite system |
| title_fullStr | Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite system |
| title_full_unstemmed | Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite system |
| title_short | Site-selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid-grafted organic/inorganic hybrid nanocomposite system |
| title_sort | site selective oral delivery of therapeutic antibodies to the inflamed colon via a folic acid grafted organic inorganic hybrid nanocomposite system |
| topic | Infliximab Aminoclay Colonic delivery TNF-α Inflammation Folate receptor |
| url | http://www.sciencedirect.com/science/article/pii/S221138352200274X |
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