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Caproyl-Modified G2 PAMAM Dendrimer (G2-AC) Nanocomplexes Increases the Pulmonary Absorption of Insulin

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Abstract

We aimed to investigate the absorption-enhancing effect (AEE) of caproyl-modified G2 PAMAM dendrimer (G2-AC) on peptide and protein drugs via the pulmonary route. In this study, G2 PAMAM dendrimer conjugates modified with caproic acid was synthesized, the pulmonary absorption of insulin as models with or without G2-AC were evaluated. The results indicated that G2-AC6 exhibited a greatest AEE for insulin in various caproylation levels of G2-AC. G2-AC6 could significantly enhance the absorption of insulin, and the AEE of G2-AC6 was concentration-dependent. In toxicity tests, G2-AC6 displayed no measurable cytotoxicity to the pulmonary membranes over a concentration range from 0.1% (w/v) to 1.0% (w/v). Measurements of the TEER and permeability showed that G2-AC6 significantly reduced the TEER value of CF and increased its Papp value. The results suggested that G2-AC6 could cross epithelial cells by means of a combination of paracellular and transcellular pathways. These findings suggested G2-AC6 at lower concentrations (below 1.0%, w/v) might be promising absorption enhancers for increasing the pulmonary absorption of peptide and protein drugs.

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Acknowledgments

The authors would like to thank the financial support of these programs.

Funding

This work was funded by National Natural Science Foundation of China (Grant No. 31860266). This study was also supported in part by Guangxi Provincial Natural Science Foundation of China (Grant No. 2018GXNSFAA281125).

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Authors and Affiliations

  1. College of Pharmacy, Guilin Medical University, Guilin, 541004, China

    Chengyun Yan, Yuefeng Wang, Ying Liao & Yueyi Deng

  2. First Affiliated Hospital of Jiamusi University, Jiamusi of University, Jiamusi, 154000, China

    Jiwei Gu

  3. College of Pharmacy, Jiamusi of University, Jiamusi, 154000, China

    Yuguang Lv & Weiguo Shi

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  1. Chengyun Yan
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  2. Jiwei Gu
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  3. Yuguang Lv
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  4. Weiguo Shi
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  5. Yuefeng Wang
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  6. Ying Liao
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  7. Yueyi Deng
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Correspondence to Chengyun Yan.

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Yan, C., Gu, J., Lv, Y. et al. Caproyl-Modified G2 PAMAM Dendrimer (G2-AC) Nanocomplexes Increases the Pulmonary Absorption of Insulin. AAPS PharmSciTech 20, 298 (2019). https://doi.org/10.1208/s12249-019-1505-x

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  • DOI: https://doi.org/10.1208/s12249-019-1505-x

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