Efficacy of Nanofiber Sheets Incorporating Lenvatinib in a Hepatocellular Carcinoma Xenograft Model

• Published in: Nanomaterials (Basel, Switzerland) Vol. 12; no. 8; p. 1364
• Main Authors: Yoshida, Terufumi, Kaibori, Masaki, Fujisawa, Nanami, Ishizuka, Mariko, Sumiyama, Fusao, Hatta, Masahiko, Kosaka, Hisashi, Matsui, Kosuke, Suzuki, Kensuke, Akama, Tomoya O., Katano, Tayo, Yoshii, Kengo, Ebara, Mitsuhiro, Sekimoto, Mitsugu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.04.2022; MDPI
• Subjects: Animals; Antibodies; Anticancer properties; Antitumor activity; Body weight; Cancer therapies; Controlled release; Drug delivery; drug delivery system; Drug delivery systems; Drug dosages; electrospun nanofiber sheet; FDA approval; Hepatitis; Hepatocellular carcinoma; HuH-7; lenvatinib; Liver cancer; Nanofibers; Oral administration; poly ε-caprolactone; Polycaprolactone; Prolongation; Sheets; Signal transduction; Survival; Sustained release; Tumors; Vascular endothelial growth factor; Xenografts; Xenotransplantation; United States > US; Japan; HuH-7; electrospun nanofiber sheet; drug delivery system; lenvatinib; poly ε-caprolactone
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano12081364

Lenvatinib has a high response rate in unresectable advanced hepatocellular carcinoma (HCC). In this study, we investigated whether lenvatinib-incorporating poly(ε-caprolactone) sheets (lenvatinib sheets) as a drug delivery system (DDS) exerted antitumor effects in a murine HCC model. The lenvatinib sheets were designed for sustained release of approximately 1 mg lenvatinib for 14 days. For 14 days, 1 mg lenvatinib was orally administered to mice. Then, we compared the antitumor effects of lenvatinib sheets with those of oral lenvatinib. The tumor volume, body weight, and serum lenvatinib level were measured for 14 days. A peritoneal dissemination model was established to examine the survival prolongation effect of the lenvatinib sheets. Tumor growth was significantly inhibited in the lenvatinib sheet group compared with that in the no treatment and oral groups. The antitumor effect was significantly higher in the lenvatinib sheet group. Regardless of the insertion site, the serum lenvatinib levels were maintained and showed similar antitumor effects. The mitotic index was significantly inhibited in the lenvatinib sheet group compared with that in the control group. Furthermore, lenvatinib sheets improved the 30-day survival. Lenvatinib sheets showed sufficient antitumor effects and may serve as an effective novel DDS for advanced HCC.