School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China.
Engineering Research Center of Bio-Process, Ministry of Education, Hefei University of Technology, Hefei, 230009, China.
Macromol Biosci. 2022 Jul;22(7):e2100493. doi: 10.1002/mabi.202100493. Epub 2022 Mar 25.
Oral administration of insulin faces multiple biological challenges, such as varied digestive environments, mucin exclusion, and low epithelial cells' absorption. In the present study, a hyaluronic acid (HA)-coated chitosan (CS) nanoparticle (HCP) delivery system is fabricated for insulin oral delivery. It is hypothesized that the developed nanoparticles will protect insulin from digestive degradation, promote intestinal epithelial cell absorption, and exert strong in vivo hyperglycemic ability. Nanoparticles formulated by CS and sodium tripolyphosphate (TPP) are optimized to form the core nanoparticles (CNPs). HA is further applied to coat CNP (HCP) to improve stability, reduce enzymatic degradation, and promote absorption of insulin. HCP promotes insulin uptake by Caco-2 cells, absorbs less mucin, and improves intestinal absorption. Moreover, an in vivo test demonstrates that oral administration of insulin-loaded HCP exerts strong and continuous hyperthermia effect (with a pharmacological availability (PA) of 13.8%). In summary, HCP is a promising delivery platform for insulin oral administration in terms of protecting insulin during digestion, facilitating its absorption and ultimately promoting its oral bioavailability.
胰岛素的口服给药面临多种生物学挑战,例如不同的消化环境、黏液排斥和低上皮细胞吸收。在本研究中,构建了一种透明质酸(HA)包覆壳聚糖(CS)纳米颗粒(HCP)给药系统,用于胰岛素的口服递送。假设开发的纳米颗粒将保护胰岛素免受消化降解,促进肠道上皮细胞吸收,并发挥强大的体内降血糖能力。通过 CS 和三聚磷酸钠(TPP)配制的纳米颗粒被优化以形成核纳米颗粒(CNPs)。进一步应用 HA 对 CNP(HCP)进行涂层以提高稳定性、减少酶降解并促进胰岛素吸收。HCP 促进 Caco-2 细胞摄取胰岛素,吸收较少的黏液,并改善肠道吸收。此外,体内试验表明,负载胰岛素的 HCP 的口服给药具有强大且持续的降血糖作用(具有 13.8%的药效学(PA))。总之,HCP 是一种有前途的胰岛素口服给药递送平台,可在消化过程中保护胰岛素,促进其吸收,最终提高其口服生物利用度。
ACS Appl Mater Interfaces. 2015-7-9
Adv Healthc Mater. 2018-7-8
J Control Release. 2009-4-17
Eur J Pharm Sci. 2010-12-21
Front Bioeng Biotechnol. 2025-4-25
IET Nanobiotechnol. 2024
J Nanobiotechnology. 2024-1-3
J Nanobiotechnology. 2022-9-24
J Control Release. 2022-11