Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization
Abstract Background There is a strong need for non-invasive and patient-friendly delivery systems of protein drugs for long-term therapy. However, oral delivery of protein drugs is a big challenge due to many barriers including instability in the gastrointestinal (GI) tract and low permeability. To...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-020-00750-y |
| _version_ | 1828138070453518336 |
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| author | Jae Geun Song Sang Hoon Lee Hyo-Kyung Han |
| author_facet | Jae Geun Song Sang Hoon Lee Hyo-Kyung Han |
| author_sort | Jae Geun Song |
| collection | DOAJ |
| description | Abstract Background There is a strong need for non-invasive and patient-friendly delivery systems of protein drugs for long-term therapy. However, oral delivery of protein drugs is a big challenge due to many barriers including instability in the gastrointestinal (GI) tract and low permeability. To overcome the absorption barriers in GI tract and improve the patient compliance, this study aimed to develop an M cell targeted-nanocomposite delivery system of protein drugs. Results An aminoclay-protein core complex (AC-Ins) was prepared by using insulin as a model protein and then sequentially coated with Ulex europaeus agglutinin 1 (UEA-1) for M-cell targeting and the pH sensitive polymer, Eudragit® L100 (EUAC-Ins). All nanoparticles were obtained with a high entrapment efficiency (> 90%) and their structural characteristics were confirmed by Fourier transform-infrared spectroscopy, energy dispersive X-ray spectroscopy, and circular dichroism. Among the developed nanoparticles, EUAC-Ins effectively suppressed drug release at pH 1.2, while rapidly released drugs at pH 6.8 due to dissolution of the outer coating layer. The conformational stability of insulin entrapped in EUAC-Ins was well maintained in the presence of proteolytic enzymes. Compared to free insulin, EUAC-Ins increased the membrane transport of insulin by 4.4-fold in M cells. In parallel, oral administration of EUAC-Ins in mice enhanced insulin uptake by 4.1-fold in the intestinal Peyer’s patches and 2.6-fold in intestinal epithelium tissues with normal villi, compared to free insulin. Orally administered EUAC-Ins decreased significantly the blood glucose level in diabetic mice, while the effect of oral insulin solution was negligible. Conclusion An M cell targeted-ternary nanocomposite system obtained by dual coating of the aminoclay-protein core complex with UEA-1 and a pH dependent polymer is promising as an effective oral protein delivery carrier. |
| first_indexed | 2024-04-11T18:30:03Z |
| format | Article |
| id | doaj.art-b09b6092fbda4a72a88a7023b5d86053 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T18:30:03Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-b09b6092fbda4a72a88a7023b5d860532022-12-22T04:09:28ZengBMCJournal of Nanobiotechnology1477-31552021-01-0119111110.1186/s12951-020-00750-yDevelopment of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterizationJae Geun Song0Sang Hoon Lee1Hyo-Kyung Han2BK21 FOUR Team, College of Pharmacy, Dongguk University-SeoulBK21 FOUR Team, College of Pharmacy, Dongguk University-SeoulBK21 FOUR Team, College of Pharmacy, Dongguk University-SeoulAbstract Background There is a strong need for non-invasive and patient-friendly delivery systems of protein drugs for long-term therapy. However, oral delivery of protein drugs is a big challenge due to many barriers including instability in the gastrointestinal (GI) tract and low permeability. To overcome the absorption barriers in GI tract and improve the patient compliance, this study aimed to develop an M cell targeted-nanocomposite delivery system of protein drugs. Results An aminoclay-protein core complex (AC-Ins) was prepared by using insulin as a model protein and then sequentially coated with Ulex europaeus agglutinin 1 (UEA-1) for M-cell targeting and the pH sensitive polymer, Eudragit® L100 (EUAC-Ins). All nanoparticles were obtained with a high entrapment efficiency (> 90%) and their structural characteristics were confirmed by Fourier transform-infrared spectroscopy, energy dispersive X-ray spectroscopy, and circular dichroism. Among the developed nanoparticles, EUAC-Ins effectively suppressed drug release at pH 1.2, while rapidly released drugs at pH 6.8 due to dissolution of the outer coating layer. The conformational stability of insulin entrapped in EUAC-Ins was well maintained in the presence of proteolytic enzymes. Compared to free insulin, EUAC-Ins increased the membrane transport of insulin by 4.4-fold in M cells. In parallel, oral administration of EUAC-Ins in mice enhanced insulin uptake by 4.1-fold in the intestinal Peyer’s patches and 2.6-fold in intestinal epithelium tissues with normal villi, compared to free insulin. Orally administered EUAC-Ins decreased significantly the blood glucose level in diabetic mice, while the effect of oral insulin solution was negligible. Conclusion An M cell targeted-ternary nanocomposite system obtained by dual coating of the aminoclay-protein core complex with UEA-1 and a pH dependent polymer is promising as an effective oral protein delivery carrier.https://doi.org/10.1186/s12951-020-00750-yInsulinOral delivery systemM cell targetingNano-carrierAminoclay |
| spellingShingle | Jae Geun Song Sang Hoon Lee Hyo-Kyung Han Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization Journal of Nanobiotechnology Insulin Oral delivery system M cell targeting Nano-carrier Aminoclay |
| title | Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization |
| title_full | Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization |
| title_fullStr | Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization |
| title_full_unstemmed | Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization |
| title_short | Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization |
| title_sort | development of an m cell targeted nanocomposite system for effective oral protein delivery preparation in vitro and in vivo characterization |
| topic | Insulin Oral delivery system M cell targeting Nano-carrier Aminoclay |
| url | https://doi.org/10.1186/s12951-020-00750-y |
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