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Novel Mucosal Insulin Delivery Systems Based on Fusogenic Liposomes

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Purpose

Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal membranes.

Method

The FLs containing insulin were prepared by fusing insulin-loaded liposomes with inactivated SeV particles and were administered directly into the ileal, the colonic, and the rectal loops (10 IU/kg).

Results

The FL successfully enhanced the insulin absorption and induced a significant hypoglycemic effect following the colonic and the rectal administration without detectable mucosal damage. This enhancing effect of insulin absorption was further improved by increasing the amount of insulin loaded in the FL and by coencapsulating insulin-degrading enzyme inhibitor. In contrast, the insulin absorption was not increased by the ileal administration of FL because the mucous/glycocalyx layers overlaid on the ileal epithelium impede the fusion of FL to the intestinal mucosa.

Conclusion

Our results indicated that FL is a useful carrier for improving the absorption of poorly absorbable drugs, such as insulin, via the intestinal tract.

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Acknowledgments

We thank Prof. Tomoko Takahashi and Dr. Mayumi Ikegami at the Institute of Medicinal Chemistry, Hoshi University, for their support in the preparation of transverse frozen sections by cryostat.

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Authors and Affiliations

  1. Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo, 142-8501, Japan

    Takahiro Goto, Mariko Morishita, Jumpei Ehara & Kozo Takayama

  2. Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, 305-8562, Japan

    Ken Nishimura & Mahito Nakanishi

  3. Department of Virology 3, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashi-murayama, Tokyo, 208-0011, Japan

    Atsushi Kato

Authors
  1. Takahiro Goto
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  2. Mariko Morishita
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  3. Ken Nishimura
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  4. Mahito Nakanishi
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  5. Atsushi Kato
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  6. Jumpei Ehara
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  7. Kozo Takayama
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Correspondence to Mariko Morishita.

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Goto, T., Morishita, M., Nishimura, K. et al. Novel Mucosal Insulin Delivery Systems Based on Fusogenic Liposomes. Pharm Res 23, 384–391 (2006). https://doi.org/10.1007/s11095-005-9175-7

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  • DOI: https://doi.org/10.1007/s11095-005-9175-7

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