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<p>Hematological malignancies like leukemia and lymphoma are severe cancers with high relapse rates. Duvelisib (DUV) is a selective dual phosphatidylinositol 3-kinase-delta and gamma inhibitor with good potential for treating hematological malignancies. However, its application is subsided by poor solubility, permeability and side effects. Herein, we have designed a human serum albumin shell and liquid-lipid core type of nanocapsule system (DUV-NCs) for effective drug loading, enhanced circulation and improved anticancer potential of DUV. The DUV-NCs were extensively optimized with DoE, resulting in a mean particle size of 188.2 ± 1.1&#xa0;nm, PDI of 0.238 ± 0.018 and entrapment efficiency of 86.99 ± 1.40%. Moreover, a sustained release behaviour with around 80% release up to 48&#xa0;h was observed. DUV-NCs showed an IC<sub>50</sub>&#xa0;of (12.78 ± 0.66&#xa0;µg/mL), which was significantly decreased (P &lt; 0.001) than the free drug (IC<sub>50</sub>: 26.08 ± 4.04&#xa0;µg/mL) in the MOLT-4 cell line. Qualitative and quantitative cellular uptake studies in MOLT-4 cells revealed considerably higher internalization of FITC-NCs than free FITC. DUV-NC-treated groups also displayed higher ROS generation, which was also evident from the increase in apoptotic bodies in MOLT-4 cells. Pharmacokinetic studies showed a 2.07-fold increase in MRT with a 3.56-fold rise in AUC<sub>0-t</sub> from DUV-NCs compared to free DUV. The DUV-NCs were found to be safe in toxicity studies with no major alterations in biomarkers compared to the control. In conclusion, DUV-NCs is a promising strategy to deliver DUV in hematological malignancies with improved efficacy and safety.</p> Graphical Abstract <p></p>

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Human Serum Albumin-Lipid Nanocapsules of Duvelisib for Hematological Cancers: Characterization, In-Vitro Cell-Culture, Toxicity and Pharmacokinetic Studies

  • 期刊论文

  • 发表日期：

    2026年1月15日

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  • Srushti Mahajan,
  • Mayur Aalhate,
  • Anamika Sharma,
  • Suman Karadagatla,
  • Santosh Kumar Guru,
  • Pankaj Kumar Singh

摘要

Hematological malignancies like leukemia and lymphoma are severe cancers with high relapse rates. Duvelisib (DUV) is a selective dual phosphatidylinositol 3-kinase-delta and gamma inhibitor with good potential for treating hematological malignancies. However, its application is subsided by poor solubility, permeability and side effects. Herein, we have designed a human serum albumin shell and liquid-lipid core type of nanocapsule system (DUV-NCs) for effective drug loading, enhanced circulation and improved anticancer potential of DUV. The DUV-NCs were extensively optimized with DoE, resulting in a mean particle size of 188.2 ± 1.1 nm, PDI of 0.238 ± 0.018 and entrapment efficiency of 86.99 ± 1.40%. Moreover, a sustained release behaviour with around 80% release up to 48 h was observed. DUV-NCs showed an IC50 of (12.78 ± 0.66 µg/mL), which was significantly decreased (P < 0.001) than the free drug (IC50: 26.08 ± 4.04 µg/mL) in the MOLT-4 cell line. Qualitative and quantitative cellular uptake studies in MOLT-4 cells revealed considerably higher internalization of FITC-NCs than free FITC. DUV-NC-treated groups also displayed higher ROS generation, which was also evident from the increase in apoptotic bodies in MOLT-4 cells. Pharmacokinetic studies showed a 2.07-fold increase in MRT with a 3.56-fold rise in AUC0-t from DUV-NCs compared to free DUV. The DUV-NCs were found to be safe in toxicity studies with no major alterations in biomarkers compared to the control. In conclusion, DUV-NCs is a promising strategy to deliver DUV in hematological malignancies with improved efficacy and safety.

Graphical Abstract