Hyaluronic-Acid-Coated Chitosan Nanoparticles for Insulin Oral Delivery: Fabrication, Characterization, and Hypoglycemic Ability

Haishan Wu, Ting Guo, Jian Nan, Liu Yang, Guangfu Liao, Hyun Jin Park, Jinglei Li

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Article number2100493
JournalMacromolecular Bioscience
Issue number7
Publication statusPublished - 2022 Jul

Bibliographical note

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.


  • bioavailability
  • cellular uptake
  • controlled release
  • insulin

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry


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