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Preparation and characterization of CS/γ-PGA/PC complex nanoparticles for insulin oral delivery

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Abstract

In recent years, natural polyelectrolyte complex chitosan/poly-γ-glutamic acid (CS/γ-PGA) has emerged as a promising nanocarrier delivery system for drug delivery due to its non-toxic and easily degradable properties. However, tightly bound CS/γ-PGA complexes often lead to lower encapsulation efficiency of peptide drugs without coordination of metal ions. In this investigation, we find that procyanidin (PC), as a cross-linking agent, is able to combine with CS and insulin through hydrogen bonding, which significantly improve encapsulation efficiency of insulin up to 90% in CS/γ-PGA/PC complex nanoparticles (CNPs). The results of this study demonstrate that CNPs release insulin in a pH-dependent approach and greatly reduce its enzymatic degradation in vitro. The transepithelial permeability of the CNPs is 8.1-fold higher than that of native insulin via both endocytosis and paracellular passways. Further pharmacokinetic studies reveal an oral pharmacological availability of 9.81 ± 1.32% in type I diabetic rats after intragastric administration of freeze-dried CNPs which loaded in enteric-coated capsules. In consequence, CNPs not only improve oral bioavailability of insulin but also are a promising delivery platform for insulin or other peptide/protein drugs.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are greatly appreciating the Scientific Research Foundation of Wuxi City for the Returned Overseas Chinese Scholars for supporting this research work.

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Scientific Research Foundation of Wuxi City for the Returned Overseas Chinese Scholars

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Authors and Affiliations

  1. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, China

    Kedong Liu, Yun Chen, Zhaoqi Yang & Jian Jin

  2. School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China

    Kedong Liu

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  1. Kedong Liu
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  2. Yun Chen
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  3. Zhaoqi Yang
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  4. Jian Jin
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Correspondence to Zhaoqi Yang or Jian Jin.

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Contents

This work developed a novel CS/γ-PGA/PC complex nanoparticles (CNPs) for oral insulin delivery. Procyanidin (PC), as a cross-linking agent, was able to combine with CS as well as insulin through hydrogen bond which significantly improved encapsulation efficiency of insulin. The results of in vivo studies showed that freeze-dried CNPs, achieved 9.81 ± 1.32% of pharmacological availability after oral administration.

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Liu, K., Chen, Y., Yang, Z. et al. Preparation and characterization of CS/γ-PGA/PC complex nanoparticles for insulin oral delivery. Colloid Polym Sci 301, 481–490 (2023). https://doi.org/10.1007/s00396-023-05078-1

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  • DOI: https://doi.org/10.1007/s00396-023-05078-1

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