Efficient Peroral Delivery of Insulin via Vitamin B12 Modified Trimethyl Chitosan Nanoparticles

Authors

  • Zhiyang Ke Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, Sichuan University, Chengdu, P.C. China
  • Han Guo Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, Sichuan University, Chengdu, P.C. China
  • Xi Zhu Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, Sichuan University, Chengdu, P.C. China
  • Yun Jin Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, Sichuan University, Chengdu, P.C. China
  • Yuan Huang Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, Sichuan University, Chengdu, P.C. China

DOI:

https://doi.org/10.18433/J3J88Q

Abstract

PURPOSE: We investigated the effect of vitamin B12 (VB12) modification on the insulin absorption from trimethyl chitosan(TMC) nanoparticles (NPs) under the influence of mucus. METHODS: TMC and TMC-VB12 were synthesized and insulin loaded TMC/TMC-VB12 nanoparticles were prepared and characterized. Modified and unmodified nanoparticles were studied with Caco-2/HT29-MTX cell model and ligated rat ileum loop. RESULTS: Compared with unmodified NPs, VB12 modified NPs showed significantly higher drug internalization in Caco-2/HT29-MTX cell model. The internalization mechanism via VB12 mediation included caveolae and clathrin-mediated endocytosis pathway. Meanwhile, an increased transportation of drugs was observed for VB12 modified NPs, possibly due to the ligand-receptor interaction via an intrinsic factor-dependent fashion. Although the uptake and transport of VB12 modified NPs could be partially influenced by mucus, they still showed higher drug permeation through Caco-2/HT29-MTX co-cultured cells than unmodified NPs in the presence or absence of mucus. Moreover, in situ study in ligated rat ileum loop demonstrated that VB12 modified nanoparticles could reduce the residual insulin in intestinal lumen (0.59 times) and increase their absorption in epithelial tissue (4.8 times) compared with the unmodified ones. CONCLUSION: VB12 modified trimethyl chitosan nanoparticle is a promising carrier for peroral delivery of insulin.

 

This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Downloads

Download data is not yet available.

Downloads

Published

2015-05-10

How to Cite

Ke, Z., Guo, H., Zhu, X., Jin, Y., & Huang, Y. (2015). Efficient Peroral Delivery of Insulin via Vitamin B12 Modified Trimethyl Chitosan Nanoparticles. Journal of Pharmacy & Pharmaceutical Sciences, 18(2), 155–170. https://doi.org/10.18433/J3J88Q

Issue

Vol. 18 No. 2 (2015)

Section

Pharmaceutical Sciences; Review Articles

License

This is an open access journal with free of charge non-commercial download. At the time of submission, authors will be asked to transfer the copyright to the accepted article to the Journal of Pharmacy and Pharmaceutical Sciences. The author may purchase the copyright for $500 upon which he/she will have the exclusive copyright to the article. Nevertheless, acceptance of a manuscript for publication in the Journal is with the authors' approval of the terms and conditions of the Creative Commons copyright license Creative Common license (Attribution-ShareAlike) License for non-commercial uses.

CLOCKSS system has permission to collect, preserve, and serve this Archival Unit.