4.7 Article

Development of iron(II) sulfate nanoparticles produced by hot-melt extrusion and their therapeutic potentials for colon cancer

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 558, Issue -, Pages 388-395

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2019.01.018

Keywords

Antiproliferation; Apoptosis; Caco-2 cell; Hot-melt extrusion; Iron(II) sulfate; Nanoparticle

Funding

  1. Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agri-Bio industry Technology Development Program - Ministry of Agriculture, Food and Rural Affairs (MAFRA) [116073-03-2-CG000]
  2. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning
  3. Ministry of Education [NRF-2017R1E1A1A01074584, NRF-2018R1A6A1A03025582]

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Particle size reduction of FeSO4 (iron(II) sulfate, IS) from micron to nano size was achieved by a combination of hot-melt extrusion (HME) processing and the input of Span 80, Tween 80, and poly(ethylene glycol) (PEG) 6000. Conveying, kneading, and extruding steps of the HME process and a decrease in the surface tension by surfactants were introduced to produce FeSO4 nanoparticles (NPs) in an aqueous environment. The FeSO4-based NPs (ISNPs) in the dispersion were composed of FeSO4, Span 80, Tween 80, and PEG 6000 and displayed a hydrodynamic size of 350-400 nm (5-50 mg/mL ISNPs concentration range) and a spherical shape. Considering the feeding ratio of FeSO4 (20%, w/w) used for preparing the ISNPs, FeSO4 appears to be wrapped by Span 80, Tween 80, and PEG 6000 according to the results of X-ray photoelectron spectroscopy (XPS) analysis. ISNPs exhibited different thermodynamic properties from those of FeSO4 itself. In colon adenocarcinoma (Caco-2) cells, the ISNPs group exhibited enhanced antiproliferation and apoptosis potentials compared to the FeSO4 group (p < 0.05). Histological staining data of a dissected intestine after oral administration of ISNPs suggest the absence of severe intestinal toxicities compared to the control (no treatment) group. All of these results imply the feasibility of the use of the developed ISNPs for the treatment of colon cancers with oral administration.

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