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

초록

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 IC<inf>50</inf> 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. © The Author(s) under exclusive licence to The Korean Society of Pharmaceutical Sciences and Technology 2025.

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