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Back to Journal »International Journal of Nanomedicine» Volume 16
Deoxycholic acid and hyaluronic acid modified layered double hydroxide can effectively absorb oral insulin
Authors: Huang X, Han Sheng, Chen Z, Zhao Li, Wang C, Guo Q, Li Yi, Sun Yi
Published on December 1, 2021, the 2021 volume: 16 pages 7861-7873
DOI https://doi.org/10.2147/IJN.S323381
Single anonymous peer review
Editor who approved for publication: Dr. Farooq A. Shiekh
Huang Xia, 1,* Han Shangcong, 1,* Chen Zuxian, 1 Zhao Lei, 2 Wang Changduo, 1 Guo Qingyang, 3 Li Yanfeng, 1 Sun Yong 1 1 Department of Pharmacy, School of Pharmacy, Qingdao University, Qingdao, People’s Republic of China, China; 2 Lu Nan Better Pharmaceutical Co., Ltd., Linyi, People's Republic of China; 3 Fisheries College of Henan Normal University, Xinxiang, People's Republic of China *These authors made equal contributions to this work by deoxycholic acid (DCA) and hyaluronic acid (HA) Modified to increase the bioavailability of oral insulin. Method: LDH-DCA-HA was synthesized by hybridization of DCA and HA with LDH. Subsequently, insulin was loaded onto LDH-DCA-HA to form [email protected]. The in vivo and in vitro release mechanism of insulin before and after DCA-HA modification and the absorption efficiency of insulin were analyzed. Results: MTT method showed that LDH-DCA-HA and Caco-2 cells have good biocompatibility when the concentration is lower than 1000 μg/mL . Flow cytometry analysis showed that Caco-2 cells are more easily absorbed than insulin [email protection]. Measurements of transepithelial resistance indicate that [email protection] induces the reversible opening of tight cell junctions, thereby promoting their absorption. This was confirmed by laser confocal microscopy analysis, indicating that a large amount of zonula occludens-1 tight junction (TJ) protein is used in the paracellular pathway of nanoparticles. We also measured the blood glucose levels of type I diabetic mice, and found that oral [email protection] has a stable blood glucose lowering effect for 12 hours, and the range of blood glucose fluctuations after meals is very small. Immunofluorescence analysis showed that [email protected]'s strong penetration ability allows insulin to enter epithelial cells more easily than free insulin. Finally, the immunohistochemical analysis of the anti-SLC10A1 protein confirmed that the bile acid transporter receptor protein plays a key role in the function of [email protected] Conclusion: LDH nanoparticles modified with DCA and HA increase the absorption of insulin by opening the TJ of the cell Efficiency and interact with bile acid transporter receptor protein. Keywords: Nanoparticle delivery system, insulin bioavailability, hypoglycemic effect, tight junction
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