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Determining the critical quality attribute for the delivery of α–mangostin by β–cyclodextrin-based nanoparticles in cancer treatment

Polymer Journal volume 55, pages 1367–1378 (2023)Cite this article

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Abstract

We previously developed cyclodextrin-based nanoparticles by utilizing a conventional polymerization method with α-, β-, γ cyclodextrin and epichlorohydrin, which successfully encapsulated a hydrophobic xanthone compound named α-mangostin (MGS). The drug release profile of MGS showed two release modes, quick release in the early stage and slow release in the late stage, which can be characterized by the lifetimes of complexes τ1 and τ2, respectively. Although these nanoparticles satisfied the demand of the Enhancement Permeation and Retention effect, only β–cyclodextrin-based nanoparticles containing MGS exhibited anticancer efficacy in vivo. Thus, the aims of the present study are to create libraries of β–cyclodextrin-based nanoparticles (CDNPs), characterize the CDNPs and clarify the relationships between the physical parameters, release behavior, and anticancer efficacy. When surfactants were present during the polymerization process, the radius of the obtained CDNPs could exceed 10 nm. τ2 was linearly dependent on the nanoparticle density and showed a relationship with anticancer efficacy. We assumed that MGS released from CDNPs would accumulate in the tumor region if the optimal range of τ2 was approximately 90–140 h. These results suggest that τ2 can be a critical quality attribute for designing our CDNPs.

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Acknowledgements

This study is financially supported by the JST CREST program, JSPS KAKENHI: Grant-in-Aid for Scientific Research A (20H00668), Grant-in-Aid for Challenging Exploratory Research (20K20449), and Grant-in-Aid for Scientific Research (19K15394).

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Author notes

  1. These authors contributed equally: Van Thi Hong Doan, Jun Katsuki

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Kitakyushu, 1-1 Hibikino, Kitakyushu, Fukuoka, 808-0135, Japan

    Van Thi Hong Doan, Jun Katsuki, Shin Takano, Shota Fujii & Kazuo Sakurai

  2. Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Cau Giay District, Hanoi, Vietnam

    Phuong Thi Mai Nguyen

  3. Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Cau Giay District, Hanoi, Vietnam

    Phuong Thi Mai Nguyen

  4. Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University, 334 Nguyen Trai Street, Thanh Xuan District, Hanoi, Vietnam

    Van Anh Thi Nguyen & Huong Thi Thu Pham

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Correspondence to Shota Fujii or Kazuo Sakurai.

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Doan, V.T.H., Katsuki, J., Takano, S. et al. Determining the critical quality attribute for the delivery of α–mangostin by β–cyclodextrin-based nanoparticles in cancer treatment. Polym J 55, 1367–1378 (2023). https://doi.org/10.1038/s41428-023-00813-5

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