Application of temporary agglomeration of chitosan-coated nanoparticles for the treatment of lung metastasis of melanoma.

Temporary association of chitosan (CS)-coated nanoparticles (NPs) including phloretin (Phl) in the blood stream can be applied to treat lung metastasis of melanoma. Phl was entrapped in poly(d,l-lactide-co-glycolide) (PLGA) NPs as an anticancer agent, whereas CS was decorated onto the outer surfaces of the Phl-loaded PLGA NPs (PLGA/Phl NPs). CS-coated PLGA/Phl NPs (CS-PLGA/Phl NPs) with mean hydrodynamic sizes of 342 nm, spherical shapes, unimodal size distribution, positive zeta potentials, and drug encapsulation efficiency larger than 90% were prepared. The presence of the CS layers in the outer surfaces of the CS-PLGA/Phl NPs was elucidated by X-ray photoelectron spectroscopy. Upon blending of the CS-PLGA/Phl NPs with serum albumin, microscale agglomerates formed and easily dissociated into individual NPs by applying external forces. A sustained Phl release from NPs and similar antiproliferation potential of the CS-PLGA/Phl NPs to that of Phl in melanoma (B16F10) cells were observed. After multiple dosing of developed NPs in mouse models with lung metastasis of melanoma, the CS-PLGA/Phl NPs group exhibited significantly lower lung weight and number of metastasis foci than the PLGA/Phl NPs group (p < 0.05). These results suggest that the transient transformation of NPs into microscale aggregates and their facile dissociation into individual NPs can be efficiently and safely applied for the treatment of lung metastasis of melanoma.