Cationic Nanomicelles for Delivery of Plasmids Encoding Interleukin-4 and Interleukin-10 for Prevention of Autoimmune Diabetes in Mice

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Abstract

Purpose

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.

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