Multi-Compartmental Nanoparticles-in-Emulsion Formulation for Macrophage-Specific Anti-Inflammatory Gene Delivery
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
- Fujiwara, N, Kobayashi, K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4: pp. 281-286 CrossRef
- Mohan, H (2005) Textbook of pathology. Jaypee Bros, New Delhi
- Glaros, T, Larsen, M, Li, L (2009) Macrophages and fibroblasts during inflammation, tissue damage and organ injury. Front Biosci 14: pp. 3988-3993 CrossRef
- Mosser, DM (2003) The many faces of macrophage activation. J Leukoc Biol 73: pp. 209-212 CrossRef
- Martinez, FO, Sica, A, Mantovani, A, Locati, M (2008) Macrophage activation and polarization. Front Biosci. 13: pp. 453-461 CrossRef
- Tsunawaki, S, Sporn, M, Ding, A, Nathan, C (1988) Deactivation of macrophages by transforming growth factor-beta. Nature 334: pp. 260-262 CrossRef
- Asadullah, K, Sterry, W, Stephanek, K, Jasulaitis, D, Leupold, M, Audring, H, Volk, HD, Docke, WD (1998) IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Invest 101: pp. 783-794 CrossRef
- Couper, KN, Blount, DG, Riley, EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180: pp. 5771-5777
- Chernajovsky, Y, Gould, DJ, Podhajcer, OL (2004) Gene therapy for autoimmune diseases: quo vadis?. Nat Rev Immunol 4: pp. 800-811 CrossRef
- Glover, DJ, Lipps, HJ, Jans, DA (2005) Towards safe, non-viral therapeutic gene expression in humans. Nat Rev Genet 6: pp. 299-310 CrossRef
- Brown, MD, Schatzlein, AG, Uchegbu, IF (2001) Gene delivery with synthetic (non viral) carriers. Int J Pharm 229: pp. 1-21 CrossRef
- Bhavsar, MD, Amiji, MM (2007) Polymeric nano- and microparticle technologies for oral gene delivery. Expert Opin Drug Deliv 4: pp. 197-213 CrossRef
- Morille, M, Passirani, C, Vonarbourg, A, Clavreul, A, Benoit, JP (2008) Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials 29: pp. 3477-3496 CrossRef
- Bhavsar, MD, Amiji, MM (2008) Development of novel biodegradable polymeric nanoparticles-in-microsphere formulation for local plasmid DNA delivery in the gastrointestinal tract. AAPS PharmSciTech 9: pp. 288-294 CrossRef
- Bhavsar, MD, Amiji, MM (2008) Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease. Gene Ther 15: pp. 1200-1209 CrossRef
- Kaul, G, Amiji, M (2005) Tumor-targeted gene delivery using poly(ethylene glycol)-modified gelatin nanoparticles: in vitro and in vivo studies. Pharm Res 22: pp. 951-961 CrossRef
- Kaul, G, Amiji, M (2002) Long-circulating poly(ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm Res 19: pp. 1061-1067 CrossRef
- Kommareddy, S, Amiji, M (2007) Antiangiogenic gene therapy with systemically administered sFlt-1 plasmid DNA in engineered gelatin-based nanovectors. Cancer Gene Ther 14: pp. 488-498 CrossRef
- Kommareddy, S, Amiji, M (2005) Preparation and evaluation of thiol-modified gelatin nanoparticles for intracellular DNA delivery in response to glutathione. Bioconjug Chem 16: pp. 1423-1432 CrossRef
- 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.
- Magadala, P, Amiji, M (2008) Epidermal growth factor receptor-targeted gelatin-based engineered nanocarriers for DNA delivery and transfection in human pancreatic cancer cells. AAPS J 10: pp. 565-576 CrossRef
- 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
- Shahiwala, A, Amiji, MM (2008) Enhanced mucosal and systemic immune response with squalane oil-containing multiple emulsions upon intranasal and oral administration in mice. J Drug Target. 16: pp. 302-310 CrossRef
- Deshpande, D, Devalapally, H, Amiji, M (2008) Enhancement in anti-proliferative effects of paclitaxel in aortic smooth muscle cells upon co-administration with ceramide using biodegradable polymeric nanoparticles. Pharm Res 25: pp. 1936-1947 CrossRef
- Kommareddy, S, Amiji, M (2007) Poly(ethylene glycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery. Nanomedicine 3: pp. 32-42 CrossRef
- 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.
- Kommareddy S, Tiwari S, Amiji MM. Long-circulating nanovectors for tumor-specific gene delivery. Tech Canc Res Treat. 2005;4(6):615–625.
- Bhavsar, MD, Amiji, MM (2007) Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS). J Contr Release 119: pp. 339-348 CrossRef
- Bhavsar, MD, Tiwari, SB, Amiji, MM (2006) Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design. J Contr Release 110: pp. 422-430 CrossRef
- Multi-Compartmental Nanoparticles-in-Emulsion Formulation for Macrophage-Specific Anti-Inflammatory Gene Delivery
Volume 29, Issue 6 , pp 1637-1649
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- anti-inflammatory therapy
- mIL-10 transfection
- non-viral gene delivery
- Industry Sectors