title: Multi-compartmental nanoparticles-in-emulsion formulation for macrophage-specific anti-inflammatory gene delivery.
abstract: OBJECTIVE
  To develop a safe and effective non-viral vector for gene delivery and transfection in macrophages for potential anti-inflammatory therapy.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Husain
authors.initials: H
authors.lastname: Attarwala
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D015536:Down-Regulation; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D005780:Gelatin / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012450:Safflower Oil / Q000737:chemistry*; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C485184:enhanced green fluorescent protein; D014867:Water; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D012450:Safflower Oil; D005780:Gelatin