Preparation of cupric sulfate-based self-emulsifiable nanocomposites and their application to the photothermal therapy of colon adenocarcinoma.

Nanocomposites (NCs) of cupric sulfate monohydrate (CuSO4) were fabricated by hot-melt extrusion (HME) system equipped with twin screws. Micron-sized bulk powder of CuSO4 was dispersed in the mixture of surfactants (Span 80 and Tween 80) and hydrophilic polymer (polyethylene glycol (PEG) 6000) by HME process. Reduction of surface tension by surfactants and homogeneous dispersion in hydrophilic polymer along with HME technique were introduced to prepare CuSO4 NCs. Dispersion of CuSO4 NCs exhibited approximately 204 nm hydrodynamic size, unimodal size distribution, and positive zeta potential values. Encapsulation of CuSO4 in CuSO4 NCs and the physicochemical interactions between CuSO4 and pharmaceutical excipients were investigated by solid-state studies. Of note, CuSO4 NCs group exhibited higher antiproliferation efficacies, compared with bulk CuSO4, in Caco-2 (human adenocarcinoma) cells at 75 and 100 μg/mL CuSO4 concentrations (p < 0.05). Also, near-infrared laser irradiation to CuSO4 NCs group elevated the antiproliferation efficacies, compared with non-irradiation group, in Caco-2 cells. After intravenous injection in mice, CuSO4 NCs did not show severe in vivo toxicities. Developed CuSO4 NCs can be one of promising candidates of photothermal therapeutic agents for colon cancers.