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 IC50 value was observed for HAIRT- 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.

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