Abstract
To develop a safe and effective non-viral vector for gene delivery and transfection in macrophages for potential anti-inflammatory therapy. Solid nanoparticles-in-emulsion (NiE) multi-compartmental delivery system was designed using plasmid DNA-encapsulated type B gelatin nanoparticles suspended in the inner aqueous phase of safflower oil-containing water-in-oil-in-water (W/O/W) multiple emulsion. Control and NiE formulations were evaluated for DNA delivery and transfection efficiency in J774A.1 adherent murine macrophages. Using green fluorescent protein (GFP) and murine interleukin-10 (mIL-10) expressing plasmid DNA constructs, the NiE formulation was found superior in enhancing intracellular delivery and gene transfection efficiency in cells. Anti-inflammatory effects of transfected mIL-10 were examined by suppression of tumor necrosis factor-alpha (TNFα) and interleukin 1-beta (IL-1β) production in lipopolysaccharide (LPS)-stimulated cells. Overall, the results were very encouraging towards development of a macrophage-specific NiE-based multi-compartmental gene delivery strategy that can potentially affect a number of acute and chronic inflammatory diseases.
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