earticle

영어

Reversible aggregation and dissociation of chitosan (CS)-coated nanoparticles (NPs) including phloretin (Phl) after intravenous injection were elucidated to inhibit lung metastasis of melanoma in this study. Phl was encapsulated in poly(D,L-lactide-coglycolide) (PLGA) NPs as an anticancer agent, and CS was adsorbed onto the exterior surfaces of the Phl-loaded PLGA NPs (PLGA/Phl NPs). PLGA/Phl NPs (mean diameter: 194 nm; polydispersity index: 0.03; zeta potential: –37.9 mV; drug encapsulation efficiency: 79%), and CS-coated PLGA/Phl NPs (CS–PLGA/Phl NPs, mean diameter: 342 nm; polydispersity index: 0.19; zeta potential: 23.3 mV; drug encapsulation efficiency: 93%) were successfully fabricated. The deposition of the CS layers in the external surfaces of the CS–PLGA/Phl NPs was evaluated by X-ray photoelectron spectroscopy. PLGA/Phl NPs maintained their initial particle size in serum albumin, while CS–PLGA/Phl NPs exhibited the formation of micro-sized aggregates and easily disassembled into each NP by extrinsic energy. Sustained Phl release pattern from CS–PLGA/Phl NPs and equivalent antiproliferation potential of the Phl-loaded NPs to that of Phl in melanoma (B16F10) cells were confirmed. After multiple injection of designed NPs in lung metastasis mouse models of melanoma, CS– PLGA/Phl NPs group presented significantly lower lung weight and fewer metastasis foci than PLGA/Phl NPs group (p < 0.05). All these findings suggest that the reversible aggregation and dissociation mechanism of NPs can be easily applied to the therapy of lung metastasis of melanoma.