Diabetes Metab J.  2011 Aug;35(4):317-326. 10.4093/dmj.2011.35.4.317.

Polymeric Gene Delivery for Diabetic Treatment

• Kim SW

• KMID: 2281637
• DOI: http://doi.org/10.4093/dmj.2011.35.4.317

Abstract

Several polymers were used to delivery genes to diabetic animals. Polyaminobutyl glycolic acid was utilized to deliver IL-10 plasmid DNA to prevent autoimmune insulitis of non-obese diabetic (NOD) mouse. Polyethylene glycol grafted polylysine was combined with antisense glutamic acid decarboxylase (GAD) MRNA to represent GAD autoantigene expression. GLP1 and TSTA (SP-EX4) were delivered by bioreducible polymer to stop diabetic progression. Fas siRNA delivery was carried out to treat diabetic NOD mice animal.

Keyword

Il-10 plasmid DNA; GAD MRNA; SP-Ex4; FasSiRNA

MeSH Terms

Animals
Antigens, Neoplasm
DNA
Glutamate Decarboxylase
Glycolates
Histocompatibility Antigens
Interleukin-10
Mice
Mice, Inbred NOD
Plasmids
Polyethylene Glycols
Polylysine
Polymers
RNA, Messenger
RNA, Small Interfering
Transplants
Antigens, Neoplasm
DNA
Glutamate Decarboxylase
Glycolates
Histocompatibility Antigens
Interleukin-10
Polyethylene Glycols
Polylysine
Polymers
RNA, Messenger
RNA, Small Interfering

Figure

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  Fig. 1 Suppression of insulitis in NOD mice after tail vein injections of PAGA/DNA complexes (2/1, +/-) at the dose of 100 µg pCAGGS mIL-10 plasmid per mouse. Insulitis was evaluated by hematoxylin-eosin staining of more than 20 islets from each pancreas and evaluating the progression of insulitis. (A) PAGA injected group. (B) PAGA/DNA complex injected group. (C) Naked DNA injected group. (D) Insulitis grade 0. (E) Insulitis grade 2. (F) Insulitis grade 4.

• 

  Fig. 2 In vitro transfection assay in HepG2 cells for GLP-1 expression. (A) The GLP-1 levels after transfection of the PEI/pSIGLP1 complex into HepG2 cells. (B) Insulin production in isolated rat islets cocultured with pSIGLP1-transfected HepG2 cells. The graph represents the SE averages for 6 experiments. aP<0.05 compared to control, bP<0.05 compared to pSIGLP1.

• 

  Fig. 3 Delivery of PEI/pSIGLP1 in DIO mice. (A) Blood glucose level, (B) plasma GLP-1 level, and (C) plasma insulin concentration changes after PEI/pSIGLP1 injection. The DIO mice received intravenous injection of PEI only or PEI with empty plasmid or PEI with pSIGLP1 or PEI/pSIGLP1. Each group was composed of 6 rats, and the graphs represent the SE averages. aP<0.05 compared to control.

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  Fig. 4 Produced EX4 concentration with (A) PB-SP-EXP and (B) TSTA (SP-EX4) using PEI25K and ABP polymers.

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  Fig. 5 Diabetes was induced by injecting a single dose of cyclophosphamide (CY) (250 mg/kg body weight) (Day 0) prior to the administration of indicated formulations. Animals with a blood glucose level above 250 mg/dL were considered hyperglycemic (n=15).

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