title: Cationic nanomicelles for delivery of plasmids encoding interleukin-4 and interleukin-10 for prevention of autoimmune diabetes in mice.
abstract: OBJECTIVE
  To evaluate the in vivo transfection efficiency of N-acyl derivatives of low-molecular weight chitosan (LMWC) to deliver pVIVO2-mIL4-mIL10 plasmid encoding interleukin-4 (IL-4) and interleukin-10 (IL-10) in multiple, low-dose streptozotocin induced diabetic mouse model.
  
  
  METHODS
  N-acyl LMWC nanomicelles were characterized for size and charge. The pVIVO2-mIL4-mIL10/N-acyl LMWC polyplexes were injected intramuscularly in mice and compared for transfection efficiency with naked DNA and FuGENE® HD. Bicistronic pVIVO2-mIL4-mIL10 plasmid was compared with individual plasmids encoding IL-4 and IL-10 for efficacy. The levels of blood glucose and serum IL-4, IL-10, TNF-α and IFN-γ were monitored. The ability of plasmid administration to protect from insulitis and biocompatibility of N-acyl LMWC were studied.
  
  
  RESULTS
  The N-acyl LMWC led to significantly higher (p < 0.05) expression of IL-4 and IL-10 and reduced the levels of blood glucose, TNF-α and IFN-γ, especially in animals treated with pVIVO2-mIL4-mIL10 plasmid. The pancreas of pDNA/N-acyl LMWC polyplex treated animals exhibited protection from insulitis and the delivery systems were found to be biocompatible.
  
  
  CONCLUSIONS
  N-acyl derivatives of LMWC are efficient and biocompatible gene delivery vectors, and the administration of bicistronic pVIVO2-mIL4-mIL10 plasmid polyplexes can protect the pancreatic islets from insulitis, possibly due to the synergistic effect of IL-4 and IL-10 encoding plasmids.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy Nursing and Allied Sciences, North Dakota State University, Fargo, North Dakota 58102, USA.
authors.forename: Rhishikesh
authors.initials: R
authors.lastname: Mandke
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002412:Cations / Q000737:chemistry; D048271:Chitosan / Q000031:analogs & derivatives*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001786:Blood Glucose; D002412:Cations; D008823:Micelles; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D048271:Chitosan
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