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Melanoma treatment is challenging due to drug resistance mechanisms and potentially lethal adverse effects of current treatments. This study aims to investigate the association of photodynamic therapy (PDT), immunotherapy and iontophoresis for topical treatment of melanoma. Nanoemulsion loaded with zinc-phthalocyanine (ZnPc) and bevacizumab was developed. Its cytotoxicity and phototoxicity in B16F10 melanoma cells and inhibition of proliferation in CRL-9222 cells was investigated in vitro. In vivo, the influence of PDT in tumor growth was compared after its administration by iontophoresis and intratumoral injection. Nanoemulsion presented size, polydispersity and zeta potential of 184±14 nm, 0.15±0.01 and +24±3 mV, respectively. Bevacizumab increased the phototoxicity of ZnPc-nanoemulsion, decreasing the IC50 more than 3-fold and inhibiting cell migration for longer periods than in solution. Iontophoresis increased ZnPc skin penetration by 16-fold. PDT after iontophoresis reduced tumor growth at least similarly to intratumoral injection, proving to be a promising strategy for the treatment of melanoma.
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