Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport
Abstract
The present study was to demonstrate the effects of goblet cell-targeting nanoparticles on the oral absorption of insulin in vitro, ex vivo and in vivo, and identify the targeting mechanism as well as the influence of mucus. The insulin loaded nanoparticles were prepared using trimethyl chitosan chloride (TMC) modified with a CSKSSDYQC (CSK) targeting peptide. Compared with unmodified nanoparticles, the CSK peptide modification could facilitate the uptake of nanoparticles in villi, enhance the permeation of drugs across the epithelium, meanwhile, induce a significantly higher internalization of drugs via clathrin and caveolae mediated endocytosis on goblet cell-like HT29-MTX cells. In transport studies across Caco-2/HT29-MTX co-cultured cell monolayer (simulating intestinal epithelium), the CSK peptide modification also showed enhanced transport ability, even if the targeting recognition was partially affected by mucus. Moreover, it was found the existence of mucus was propitious to the transport of insulin from both modified and unmodified nanoparticles. In the pharmacological and pharmacokinetic studies in diabetic rats, the orally administrated CSK peptide modified nanoparticles produced a better hypoglycemic effect with a 1.5-fold higher relative bioavailability compared with unmodified ones. In conclusion, CSK peptide modified TMC nanoparticles showed sufficient effectiveness as goblet cell-targeting nanocarriers for oral delivery of insulin.
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Presence of CSK peptide increases bioavailability of insulin-loaded nanoparticles at targeted site, resulting in effective depression of blood glucose level.
“Hence, the presence of CSK peptide increases the bioavailability of the insulin-loaded nanoparticles at the targeted site, which results in effective depression of the blood glucose level.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [86]
Size of chitosan nanoparticles increased from 182 to 342 nm after modification with TMC, CSK, and INS, and zeta potential decreased from 10 to 3 mV.
“The size of the nanoparticle was increased from 182 to 342 nm after the nanoparticles were modified with TMC, CSK, and INS, which decreased the zeta potential from 10 to 3 mV.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [86]
CSK peptide promotes absorption of nanoparticles.
“Furthermore, greater absorption of the nanoparticles modified with CSK peptide than of unmodified nanoparticles, which signifies that the CSK peptide promotes the absorption of the nanoparticles.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [86]
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- Authors
- Jin, Y., Song, Y., Zhu, X., Zhou, D., Chen, C., Zhang, Z., & Huang, Y.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Huang, Yuan
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 33
- Issue
- 5
- Pages
- 1573-1582
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2086806495
- Cited by
- 301
- References
- 46
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 8 · 2023: 12 · 2022: 23 · 2021: 24 · 2020: 29 · 2019: 21 · 2018: 17 · 2017: 25 · 2016: 32 · 2015: 35 · 2014: 29 · 2013: 16 · 2012: 14
- FWCI
- 11.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81173010)
- National S & T Major Project of China (2009ZX09310-002)
- Youth academic leader Foundation of Sichuan province (09ZQ026-051)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- oral insulin delivery, nanoparticles, mucus, intestinal epithelium, insulin transport, clathrin-mediated endocytosis, caveolae, HT29-MTX cells, Caco-2/HT29-MTX co-culture, bioavailability, hypoglycemic effect, diabetic rats
- MeSH terms
- Administration, Oral, Amino Acid Sequence, Animals, Blood Glucose, Humans, Hypoglycemic Agents, Ileum, Insulin, Intestinal Absorption, Male, Molecular Sequence Data, Mucus, Peptides, Tissue Distribution, Drug Delivery Systems, Fluorescein-5-isothiocyanate, Cell Death, Rats, Sprague-Dawley, Caco-2 Cells, Goblet Cells, Protein Transport, Chitosan, Rats, Nanoparticles, In Vitro Techniques
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