Microneedle Patches Loaded with cRGD-Modified pH-Sensitive Hydroxycamptothecin Liposomes for Melanoma Therapy

Melanoma is one of the most common and aggressive skin malignancies with unsatisfactory treatment effects due to the serious side effects, multidrug resistance, and poor prognosis. Chemotherapeutic transdermal delivery has emerged as a highly effective and novel strategy for melanoma therapy. In this study, we chose hydrophobic 10-hydroxycamptothecin (HCPT) as a model drug and developed novel microneedle (MN) patches integrated with cRGD-modified pH-sensitive HCPT liposomes (cRGD-LP-HCPT MN patches). The approach not only enhances the drug's solubility and stability but also allows for high targeting specificity and maximizing intracellular drug accumulation in melanoma cells. The cRGD-modified pH-sensitive HCPT liposomes (cRGD-LP-HCPT) were prepared by using a thin-film hydration-ultrasonic method. cRGD-LP-HCPT exhibited high drug encapsulation efficiency (94.78%), small size (∼102.91 nm), good stability, and a profile of a rapid drug release triggered by acidic conditions. Meanwhile, it displayed higher cytotoxic effects, with an IC₅₀ value of 1 μg/mL, compared to HCPT or the liposomes without modification. Consequently, to facilitate the transdermal delivery of HCPT into deep tumor tissues, cRGD-LP-HCPT were assembled into water-soluble needle tips of the microneedles. The cRGD-LP-HCPT MN patches exhibited excellent mechanical properties. Successful needle penetration into the pig skin with a distribution at a depth of about 200 μm was observed. Furthermore, in contrast to the systemic distribution profile of intravenous cRGD-LP-IR780, cRGD-LP-IR780 MN patches led to highly localized and potent tumor-specific fluorescence with negligible exposure to normal tissues. Ultimately, this novel HCPT formulation exhibited significant antitumor efficiency and minimal side effects. These results demonstrated that the cRGD-LP-HCPT MN patch could be a promising drug delivery system for melanoma treatment in the clinic.