Polymeric excipients potentiate the anticancer activity of mitoxantrone-loaded quercetin nanoparticles in topical melanoma therapy.

Melanoma is an aggressive skin cancer caused by abnormal development of melanocytes. Here we report on a nanoparticle (NP) formulation for the anticancer drug mitoxantrone (MTX) against melanoma. The NPs were formed from the partial oxidation of quercetin to produce amphiphilic oxQCT, which was co-assembled with poly(ethylene glycol) (PEG), Pluronic F127, or D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), alongside MTX, by nanoprecipitation. MTX-loaded NPs (MTX ⊂ oxQCT/F127, MTX ⊂ oxQCT/PEG, and MTX ⊂ oxQCT/TPGS NPs) were ∼100 nm in size with low polydispersity and 80-90% drug loading efficiencies. Colloidal stability of the NPs varied as a function of the co-formulated polymer excipient. Cytotoxicity assays in the B16F10 melanoma cell line monolayers showed that free MTX was slightly more potent than the NP formulations. However, NPs co-formulated with TPGS (MTX ⊂ oxQCT/TPGS NPs) more effectively inhibited cell migration and colony formation compared to the free drug and other nanoformulations. They also demonstrated a superior ability to inhibit the growth of 3D B16F10 spheroids and facilitate in vitro accumulation of MTX in skin-mimetic Strat-M membrane compared to the free drug. In an in vivo melanoma model, MTX ⊂ oxQCT/TPGS NPs significantly suppressed tumor growth after 10 days of topical administration compared to the free drug, highlighting the promising role of oxQCT NPs in promoting the efficacy of MTX for melanoma therapy.