Multi-Compartmental Nanoparticles-in-Emulsion Formulation for Macrophage-Specific Anti-Inflammatory Gene Delivery
- 440 Downloads
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.
KEY WORDSanti-inflammatory therapy macrophage-targeted mIL-10 transfection nanoparticles-in-emulsion non-viral gene delivery
ACKNOWLEDGMENTS & DISCLOSURES
This study was supported by a grant (R01-DK080477) from the National Institute of Diabetes, Digestive Diseases, and Kidney Diseases of the National Institutes of Health. We deeply appreciate the assistance of Ms. Jing Xu with the transmission electron microscopy analysis that was performed at the Electron Microscopy Center of Northeastern University.
- 2.Mohan H. Textbook of pathology. New Delhi: Jaypee Bros; 2005.Google Scholar
- 20.Kriegel C, Amiji M. Oral TNF-alpha gene silencing using a polymeric microsphere-based delivery system for the treatment of inflammatory bowel disease. J Control Release. 2011;150:77–86.Google Scholar
- 22.Xu J, Ganesh S, Amiji M. Non-condensing polymeric nanoparticles for targeted gene and siRNA delivery. Int J Pharm. 2011. doi:10.1016/j.ijpharm.2011.05.036
- 26.Kommareddy S, Amiji MM. Protein nanospheres for gene delivery: preparation and in vitro transfection studies with gelatin nanoparticles. In: Friedmann T, Rossi J, editors. Gene Transfer: Delivery and Expression of DNA and RNA – A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 2007, Chapter 52, pp 527--540.Google Scholar
- 27.Kommareddy S, Tiwari S, Amiji MM. Long-circulating nanovectors for tumor-specific gene delivery. Tech Canc Res Treat. 2005;4(6):615–625.Google Scholar