Mucus- and pH-mediated controlled release of core-shell chitosan nanoparticles in the gastrointestinal tract for diabetes treatment

Abstract

For the successful oral delivery of peptide drugs, considerable barriers created by the harsh environment of the gastrointestinal tract, mucus, and epithelial cells must be overcome. This study was to establish a core-shell structure with chitosan (CS) nanoparticles (NP) as the core and poly-N-(2-hydroxypropyl) methacrylamide (pHPMA) as the intelligent escape shell to overcome pH and mucus barriers and improve the delivery efficiency of peptide drugs. A core-shell system (COS) composed of pHPMA-AT-1002-cys-chitosan (LRA-PA-CNPs) was prepared and used for the treatment of type 2 diabetes mellitus with the large-molecule peptide drug liraglutide (LRA). The complete COS system was observed through electron microscopy; the particle size of the LRA-PA-CNPs was approximately 160 nm; the encapsulation efficiency was approximately 69% ± 5%; the zeta potential was close to neutral; the mucus and epithelial penetration of the COS system were increased; and animal experiments showed that the COS system enhanced the oral hypoglycaemic effect of LRA.

HIGHLIGHTS

1. Intelligent escape material of poly-N-(2-hydroxypropyl) methacrylamide as the shell.

2. Core-shell nanoparticles penetrate the mucus layer and exposing the chitosan core.

3. Overcome pH and mucus barriers to improve the delivery efficiency of peptide drugs.

Graphical Abstract

Keywords:

• Oral peptide delivery
• intelligent escape material
• gastrointestinal barrier
• mucus penetration
• diabetes

Acknowledgments

The author has no other relevant statements or financial involvement with any financially related organisation or entity, or has no financial interest other than disclosure. We thank Gabrielle David, PhD, from Liwen Bianji, Edanz Group China, for editing the English text of a draft of this manuscript.

Authors’ contributions

Authors have contributed equally in this manuscript.

Ethics approval and consent to participate

All animal experiments were approved by the Experimental Animal Ethics Committee of the College of Pharmacy, Yantai University.

Consent for publication

All authors have the consent for publication.

Availability of data and materials

The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the support of Yantai University Doctoral Program (No. SM20B35) and Natural Science Foundation of Shandong Province (No. ZR2021MH395).