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Purpose <p>Non-small cell lung cancer (NSCLC) is one of the deadliest cancers, with high morbidity and mortality worldwide. Nanotechnology-based targeted therapy is a promising strategy to improve the pharmacokinetics and antitumor efficacy of antitumor drugs in NSCLC.</p> Methods <p>The present study is focused on the pharmacokinetics and in vivo antitumor investigations of a novel palbociclib (PAL)- and regorafenib (REG)-loaded d-α-tocopheryl polyethylene glycol succinate and poly lactic acid (TPGS-PLA) nano micelles (PAL-REG-TPGS-PLAM) towards NSCLC and its comparison with monotherapies (PAL-TPGS-PLAM and REG-TPGS-PLAM) and drug dispersions (PAL-REG-Dispersion, PAL-Dispersion, and REG-Dispersion). Additionally, histopathological investigations of major organs were performed to evaluate the cytotoxicity of the prepared formulations.</p> Results <p>PAL-REG-TPGS-PLAM exhibited a sustained release pattern, with 71.13% and 53.71% of PAL and REG, respectively, released after 48&#xa0;h at pH 6.8. Moreover, a significant decrease in cell viability was observed in H1299 (26.20%) and HeLa (3.66%) cells. Similarly, a pharmacokinetic study showed a prolonged blood circulation time of PAL-REG-TPGS-PLAM in rats, thereby demonstrating enhanced bioavailability. Additionally, PAL-REG-TPGS-PLAM significantly reduced tumor weight (0.09&#xa0;g) and tumor volume (35.74 mm<sup>3</sup>) when compared with the tumor weight (0.45&#xa0;g) and tumor volume (999.0 mm<sup>3</sup>) of the untreated group in a rat model of NSCLC. Furthermore, the body weight was maintained throughout the study period, indicating no risk of toxicity, which was confirmed by the improved survival rate. Histopathological analysis of the lungs, liver, and kidneys revealed the safety of PAL-REG-TPGS-PLAM in rats.</p> Conclusion <p>These results suggest that PAL-REG-TPGS-PLAM has the potential to strengthen the antitumor effectiveness owing to its sustained release, improved bioavailability, targeted drug delivery, and synergistic antitumor effects.</p>

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Palbociclib- and regorafenib-loaded nanomicelles for the treatment of non-small cell lung cancer: pharmacokinetic and antitumor evaluations

  • 期刊论文

  • 发表日期：

    2025年6月20日

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  • Maimoona Malik,
  • Fareeha Anwar,
  • Luciana Dini,
  • Ali H. Alamri,
  • Adel Al Fatease,
  • Ahmed A. Lahiq,
  • Saud Alqahtani,
  • Sung Giu Jin,
  • Han Gon Choi,
  • Fakhar ud Din

摘要

Purpose

Non-small cell lung cancer (NSCLC) is one of the deadliest cancers, with high morbidity and mortality worldwide. Nanotechnology-based targeted therapy is a promising strategy to improve the pharmacokinetics and antitumor efficacy of antitumor drugs in NSCLC.

Methods

The present study is focused on the pharmacokinetics and in vivo antitumor investigations of a novel palbociclib (PAL)- and regorafenib (REG)-loaded d-α-tocopheryl polyethylene glycol succinate and poly lactic acid (TPGS-PLA) nano micelles (PAL-REG-TPGS-PLAM) towards NSCLC and its comparison with monotherapies (PAL-TPGS-PLAM and REG-TPGS-PLAM) and drug dispersions (PAL-REG-Dispersion, PAL-Dispersion, and REG-Dispersion). Additionally, histopathological investigations of major organs were performed to evaluate the cytotoxicity of the prepared formulations.

Results

PAL-REG-TPGS-PLAM exhibited a sustained release pattern, with 71.13% and 53.71% of PAL and REG, respectively, released after 48 h at pH 6.8. Moreover, a significant decrease in cell viability was observed in H1299 (26.20%) and HeLa (3.66%) cells. Similarly, a pharmacokinetic study showed a prolonged blood circulation time of PAL-REG-TPGS-PLAM in rats, thereby demonstrating enhanced bioavailability. Additionally, PAL-REG-TPGS-PLAM significantly reduced tumor weight (0.09 g) and tumor volume (35.74 mm3) when compared with the tumor weight (0.45 g) and tumor volume (999.0 mm3) of the untreated group in a rat model of NSCLC. Furthermore, the body weight was maintained throughout the study period, indicating no risk of toxicity, which was confirmed by the improved survival rate. Histopathological analysis of the lungs, liver, and kidneys revealed the safety of PAL-REG-TPGS-PLAM in rats.

Conclusion

These results suggest that PAL-REG-TPGS-PLAM has the potential to strengthen the antitumor effectiveness owing to its sustained release, improved bioavailability, targeted drug delivery, and synergistic antitumor effects.