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

Abstract

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.

Keywords: Colon adenocarcinoma; Cupric sulfate; Hot-melt extrusion; Nanocomposite; Photothermal therapy.