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<p>Hepatocellular carcinoma (HCC) is a primary liver cancer that frequently develops resistance to anticancer drugs, leading to therapeutic failure. Gefitinib (GEF) is an EGFR inhibitor that has shown therapeutic efficacy against liver cancer; however, monotherapy has shown less effect due to the development of resistance. Betulin (BET) is a natural compound that exhibits hepatoprotective effects due to its antioxidant and anti-inflammatory properties. Research has shown that the combination of GEF and BET exhibits a synergistic effect; however, their clinical application remains challenging because of their poor solubility, bioavailability, and inadequate targeting at the tumor site. Therefore, this study focused on developing a liposomal nanoformulation loaded with GEF and BET using the ethanol injection method and optimized via BBD. GEF and BET-loaded liposomal formulations were prepared separately and mixed to form GEF-BET-Lipo. Furthermore, to achieve targeted delivery, we developed GEF-Lf-Lipo and BET-Lf-Lipo, in which lactoferrin (Lf) was used for site-specific targeting and therapeutic efficacy. GEF-Lf-Lipo and BET-Lf-Lipo were mixed to form GEF-BET-Lf-Lipo. Additionally, the basic characterization of both liposomal formulations was conducted. GEF-BET-Lf-Lipo showed significantly higher cytotoxicity than GEF-BET-Lipo and mixture of GEF-BET. The findings suggest that the GEF-BET-Lf-Lipo could be an effective carrier for delivering GEF and BET to the target site, representing a promising approach for treating HCC. Moreover, in vivo animal experiments will help to reveal the therapeutic potential of the targeted liposomes.</p>

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Development of Betulin and Gefitinib-Loaded Lactoferrin Decorated Liposomes against Hepatocellular Carcinoma

  • 期刊论文

  • 发表日期：

    2026年2月12日

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  • Amita Singh,
  • Vipin Kumar,
  • Km Prachi,
  • Nitin Rajan,
  • Anurag Kumar Gautam,
  • Sanjay Singh,
  • Vijayakumar Mahalingam Rajamanickam

摘要

Hepatocellular carcinoma (HCC) is a primary liver cancer that frequently develops resistance to anticancer drugs, leading to therapeutic failure. Gefitinib (GEF) is an EGFR inhibitor that has shown therapeutic efficacy against liver cancer; however, monotherapy has shown less effect due to the development of resistance. Betulin (BET) is a natural compound that exhibits hepatoprotective effects due to its antioxidant and anti-inflammatory properties. Research has shown that the combination of GEF and BET exhibits a synergistic effect; however, their clinical application remains challenging because of their poor solubility, bioavailability, and inadequate targeting at the tumor site. Therefore, this study focused on developing a liposomal nanoformulation loaded with GEF and BET using the ethanol injection method and optimized via BBD. GEF and BET-loaded liposomal formulations were prepared separately and mixed to form GEF-BET-Lipo. Furthermore, to achieve targeted delivery, we developed GEF-Lf-Lipo and BET-Lf-Lipo, in which lactoferrin (Lf) was used for site-specific targeting and therapeutic efficacy. GEF-Lf-Lipo and BET-Lf-Lipo were mixed to form GEF-BET-Lf-Lipo. Additionally, the basic characterization of both liposomal formulations was conducted. GEF-BET-Lf-Lipo showed significantly higher cytotoxicity than GEF-BET-Lipo and mixture of GEF-BET. The findings suggest that the GEF-BET-Lf-Lipo could be an effective carrier for delivering GEF and BET to the target site, representing a promising approach for treating HCC. Moreover, in vivo animal experiments will help to reveal the therapeutic potential of the targeted liposomes.