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Purpose <p>Melanoma is the deadliest and most refractory type of skin cancer, with a high mortality rate and resistance to available therapies. Irinotecan (IRT), a camptothecin derivative and a potent antitumor agent, belongs to the topoisomerase I inhibitor class and is associated with severe adverse effects.</p> Methods <p>Herein, a polymeric delivery system (PNPs) with IRT encapsulated in zein (ZE) and hyaluronic acid (HA) was prepared (HA-IRT-ZE PNPs) to overcome drug-related challenges. HA-IRT-ZE PNPs were optimized using Box Behnken Design and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD) and Differential scanning calorimetry (DSC). Moreover, in vitro cytotoxicity, pharmacokinetics and in vivo antitumor analyses were executed.</p> Results <p>The optimized nanoparticles demonstrated spherical morphology with particle size of 163.5 nm, polydispersity index of 0.20, zeta potential of −35.8 mV and percent entrapment efficiency (%EE) of 90.14%. FTIR results confirmed compatibility of all the components, whereas DSC and XRD displayed encapsulation of the drug within the nanoparticles and amorphous form conversion. A pH-responsive and controlled release pattern of IRT was observed from the nanoparticles with no hemolytic effect. Furthermore, decreased cancer cell viability with a 3.7-fold lower IC<sub>50</sub> value was observed for HA-IRT-ZE PNPs. Additionally, nanoparticles showed 4-fold enhanced bioavailability of IRT and improved antitumor efficacy with a reduction in tumor volume.</p> Conclusion <p>Results suggested these biopolymeric nanoparticles may be efficiently used for pH-responsive release, enhanced bioavailability and tumor targeting.</p>

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Unveiling the treatment potential of irinotecan-loaded biopolymeric nanocarrier system in skin cancer via targeting CD44 receptors

  • 期刊论文

  • 发表日期：

    2025年11月28日

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  • Sibgha Batool,
  • Ghazala Ishrat,
  • Omer Mustapha,
  • Ali H. Alamri,
  • Adel Al Fatease,
  • Zahrah Ali Asiri,
  • Ahmed Abdullah Al Awadh,
  • Han-Gon Choi,
  • Fakhar Ud Din

摘要

Purpose

Melanoma is the deadliest and most refractory type of skin cancer, with a high mortality rate and resistance to available therapies. Irinotecan (IRT), a camptothecin derivative and a potent antitumor agent, belongs to the topoisomerase I inhibitor class and is associated with severe adverse effects.

Methods

Herein, a polymeric delivery system (PNPs) with IRT encapsulated in zein (ZE) and hyaluronic acid (HA) was prepared (HA-IRT-ZE PNPs) to overcome drug-related challenges. HA-IRT-ZE PNPs were optimized using Box Behnken Design and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD) and Differential scanning calorimetry (DSC). Moreover, in vitro cytotoxicity, pharmacokinetics and in vivo antitumor analyses were executed.

Results

The optimized nanoparticles demonstrated spherical morphology with particle size of 163.5 nm, polydispersity index of 0.20, zeta potential of −35.8 mV and percent entrapment efficiency (%EE) of 90.14%. FTIR results confirmed compatibility of all the components, whereas DSC and XRD displayed encapsulation of the drug within the nanoparticles and amorphous form conversion. A pH-responsive and controlled release pattern of IRT was observed from the nanoparticles with no hemolytic effect. Furthermore, decreased cancer cell viability with a 3.7-fold lower IC50 value was observed for HA-IRT-ZE PNPs. Additionally, nanoparticles showed 4-fold enhanced bioavailability of IRT and improved antitumor efficacy with a reduction in tumor volume.

Conclusion

Results suggested these biopolymeric nanoparticles may be efficiently used for pH-responsive release, enhanced bioavailability and tumor targeting.