β-Cyclodextrin/dialdehyde glucan-coated keratin nanoparticles for oral delivery of insulin
Successful oral insulin administration can considerably enhance the quality of life (QOL) of diabetes patients who must frequently take insulin injections. However, Oral insulin administration is seriously hampered by gastrointestinal enzymes, wide pH range, mucus and mucosal layers, which limit ins...
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Veröffentlicht in: | International journal of biological macromolecules 2024-09, Vol.276 (Pt 2), p.133805, Article 133805 |
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Sprache: | eng |
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Zusammenfassung: | Successful oral insulin administration can considerably enhance the quality of life (QOL) of diabetes patients who must frequently take insulin injections. However, Oral insulin administration is seriously hampered by gastrointestinal enzymes, wide pH range, mucus and mucosal layers, which limit insulin oral bioavailability to ≤2 %. Herein, we developed a simple, inexpensive and safe dual β-cyclodextrin/dialdehyde glucan-coated keratin nanoparticle (β-CD-K-IN-DG). The resulted β-CD-K-IN-DG not only gave the ultra-high insulin loading (encapsulation efficiency (98.52 %)), but also protected insulin from acid and enzymatic degradation. This β-CD-K-IN-DG had a notable hypoglycemic effect, there was almost 80 % insulin release after 4 h of incubation under hyperglycemic conditions. Ex vivo results confirmed that β-CD-K-IN-DG possessed high mucus-penetration ability. Transepithelial transport and uptake mechanism studies revealed that bypass transport pathway and endocytosis promoted β-CD-K-IN-DG entered intestinal epithelial cells, thus increased the bioavailability of insulin (12.27 %). The improved stability of insulin during in vivo transport implied that β-CD-K-IN-DG might be a potential tool for the effective oral insulin administration.
The β-CD-K-IN-DG were produced utilizing the self-assembly method. The β-CD-K-IN-DG achieved controlled insulin release under hyperglycemic conditions, leading to a notable hypoglycemic effect and a high oral bioavailability. [Display omitted]
•β-CD-K-IN-DG had ultra-high insulin loading (98.52 %) and showed high mucus-penetration ability and oral bioavailability (12.27 %). |
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ISSN: | 0141-8130 1879-0003 1879-0003 |
DOI: | 10.1016/j.ijbiomac.2024.133805 |