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Absorption-Enhancing Mechanisms of Capryol 90, a Novel Absorption Enhancer, for Improving the Intestinal Absorption of Poorly Absorbed Drugs: Contributions to Trans- or Para-Cellular Pathways

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Abstract

Purpose

We have previously reported that Capryol 90 improves the intestinal absorption of insulin, a peptide drug, without causing serious damage to the intestinal epithelium. However, the effects of Capryol 90 and its related formulations on the intestinal absorption of other drugs, and their absorption-enhancing mechanisms are still unclear. The aim of this study is to evaluate the effects of Capryol 90 and its related formulations on the intestinal absorption of drugs and elucidate their absorption-enhancing mechanisms.

Methods

The intestinal absorption of 5(6)-carboxyfluorescein, fluorescein isothiocyanate-dextrans, and alendronate was evaluated using an in situ closed loop method. Brush border membrane vesicles (BBMVs) were labeled with fluorescent probes, and the fluidity of membrane was evaluated by a fluorescence depolarization method. The expression levels of tight junction (TJ) proteins were measured using a Western blot method and immunofluorescence staining.

Results

Among the tested excipients, Capryol 90 significantly improved the small and large intestinal absorption of drugs. In mechanistic studies, Capryol 90 increased the membrane fluidity of lipid bilayers in BBMVs. Additionally, Capryol 90 decreased the expression levels of TJ-associated proteins, namely claudin-4, occludin, and ZO-1.

Conclusions

Capryol 90 is an effective absorption enhancer for improving the intestinal absorption of poorly absorbed drugs via both transcellular and paracellular pathways.

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Declarations of Interest

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Biopharmaceutics, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-Ku, Kyoto, 607-8414, Japan

    Hiroki Ukai, Ayako Imanishi, Ayaka Kaneda, Erika Kimura, Miku Koyama, Masaki Morishita, Hidemasa Katsumi & Akira Yamamoto

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  1. Hiroki Ukai
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  2. Ayako Imanishi
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Correspondence to Akira Yamamoto.

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Ukai, H., Imanishi, A., Kaneda, A. et al. Absorption-Enhancing Mechanisms of Capryol 90, a Novel Absorption Enhancer, for Improving the Intestinal Absorption of Poorly Absorbed Drugs: Contributions to Trans- or Para-Cellular Pathways. Pharm Res 37, 248 (2020). https://doi.org/10.1007/s11095-020-02963-0

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