TY - JOUR
T1 - Hyaluronic-Acid-Coated Chitosan Nanoparticles for Insulin Oral Delivery
T2 - Fabrication, Characterization, and Hypoglycemic Ability
AU - Wu, Haishan
AU - Guo, Ting
AU - Nan, Jian
AU - Yang, Liu
AU - Liao, Guangfu
AU - Park, Hyun Jin
AU - Li, Jinglei
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China (Grant No. 31700015), Fundamental Research Funds for the Central Universities (Grant No. JZ2018HGTB0244), and Anhui Natural Science Foundation (Grant No. 1808085QC66).
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - bioavailability
KW - cellular uptake
KW - controlled release
KW - insulin
UR - http://www.scopus.com/inward/record.url?scp=85127150238&partnerID=8YFLogxK
U2 - 10.1002/mabi.202100493
DO - 10.1002/mabi.202100493
M3 - Article
C2 - 35182103
AN - SCOPUS:85127150238
SN - 1616-5187
VL - 22
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 7
M1 - 2100493
ER -