A novel approach to oral delivery of insulin by conjugating with low molecular weight chitosan
Abstract
A new oral delivery system for insulin was developed aiming to improve bioavailability based on a conjugate between insulin and low molecular weight chitosan (LMWC) of narrow molecular weight distribution. The conjugate was synthesized from the reaction between site-specifically modified insulin at the lysine residue of the B-chain and sulfhydryl-modified LMWC. To investigate the effect of MWs of LMWC on oral bioavailability of insulin, various LMWCs (3, 6, 9, and 13k average MW) with narrow MW distribution were used to synthesize LMWC-insulin conjugates. The content of insulin in the LMWC-insulin conjugates was calculated by UV spectrophotometer: 62%, 44%, 38%, and 29% for 3, 6, 9, and 13 kDa LMWC, respectively. The biological activity of insulin in LMWC(6k)-insulin conjugate in vivo was 43 ± 0.7%. LMWC-insulin conjugates after oral administration to diabetic rat models could control blood glucose levels effectively for several hours. Of those conjugates, LMWC(9k)-insulin exhibited the highest pharmacodynamic bioavailability of 3.7 ± 0.3% relative to that of subcutaneously (s.c.) injected insulin (100%).
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Insulin administered by injections generates peripheral hyperinsulinemia, which leads to hypoglycemia, cancer, atherosclerosis, and peripheral hypertension.
“Insulin is administrated into systemic circulation directly by injections, generating peripheral hyperinsulinemia, which leads to hypoglycemia, cancer, atherosclerosis, and peripheral hypertension (Lee et al., 2010).”
From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Lee et al., 2010
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- Authors
- Lee, E., Lee, J., & Jon, S.
- Affiliations
- Gwangju Institute of Science and Technology (KR)
- Corresponding author
- Jon, Sangyong
- ORCID
- Jon, Sangyong
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-09-17
- Volume
- 21
- Issue
- 10
- Pages
- 1720-1723
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W1981058015
- Cited by
- 63
- References
- 22
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 3 · 2015: 8 · 2014: 9 · 2013: 7 · 2012: 3
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioconjugate Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- oral insulin delivery, insulin, low molecular weight chitosan, site-specific conjugation, molecular weight distribution, oral bioavailability, glycemic control, diabetic rats
- MeSH terms
- Administration, Oral, Animals, Biological Availability, Blood Glucose, Chromatography, High Pressure Liquid, Diabetes Mellitus, Feasibility Studies, Insulin, Molecular Weight, Drug Design, Drug Delivery Systems, Chitosan, Rats
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