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Membrane Rigidity Determined by Atomic Force Microscopy Is a Parameter of the Permeability of Liposomal Membranes to the Hydrophilic Compound Calcein

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Abstract

We determined the permeability coefficient of a model hydrophilic drug, calcein, encapsulated within saturated lipid-based nano-sized liposomes of various lipid profiles. We demonstrated that the addition of cholesterol to liposomes containing saturated lipids increased the permeability of the liposomal membrane to calcein via a decrease in the membrane bending modulus, as determined by means of atomic force microscopy. We found an inverse correlation between the membrane bending modulus of saturated lipid-based nano-sized liposomes and the permeability coefficient of encapsulated calcein, demonstrating that bending modulus, as determined by means of atomic force microscopy, is a quantitative parameter describing the permeability of liposomal membranes to calcein.

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Acknowledgments

This work was supported, in part, by funding from the Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics project of the Japan Agency for Medical Research and Development (AMED). This work was also supported by the Research Resident Program from AMED.

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Authors and Affiliations

  1. Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan

    Yuki Takechi-Haraya

  2. Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

    Yuki Takechi-Haraya, Kumiko Sakai-Kato & Yukihiro Goda

Authors
  1. Yuki Takechi-Haraya
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  2. Kumiko Sakai-Kato
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  3. Yukihiro Goda
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Correspondence to Kumiko Sakai-Kato.

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Takechi-Haraya, Y., Sakai-Kato, K. & Goda, Y. Membrane Rigidity Determined by Atomic Force Microscopy Is a Parameter of the Permeability of Liposomal Membranes to the Hydrophilic Compound Calcein. AAPS PharmSciTech 18, 1887–1893 (2017). https://doi.org/10.1208/s12249-016-0624-x

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  • DOI: https://doi.org/10.1208/s12249-016-0624-x

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