Prevention of autoimmune insulitis by delivery of interleukin-4 plasmid using a soluble and biodegradable polymeric carrier.
OBJECTIVE
We delivered interleukin-4 (IL-4) plasmid (pCAGGS-IL-4) using the biodegradable polymer, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA), to prevent autoimmune insulitis in NOD mice.


METHODS
The pCAGGS-IL-4/PAGA complex was transfected to 293T cells. The expression level of IL-4 was measured by ELISA. The pCAGGS IL-4/PAGA complex was injected once to NOD mice intravenously at the age of 4 weeks. RT-PCR was performed to evaluate the level of the IL-4 mRNA in the liver. At 6 weeks after the injection, the grade of insulitis of the mice was evaluated by double blind methods.


RESULTS
In vitro transfecton assays showed that PAGA enhanced the expression of IL-4 in 293T cells. RT-PCR of the liver showed that IL-4 was expressed highest in the complex injected group. In the plasmid/PAGA complex injected group, the prevalence of severe insulitis in NOD mice was markedly improved, suggesting that PAGA enhanced the delivery of IL-4 plasmid.


CONCLUSIONS
The pCAGGS-IL-4/PAGA complex is an effective system to prevent autoimmune insulitis in NOD mice and applicable for the prevention of autoimmune diabetes.
Lee
Minhyung
M
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84112, USA. minhyung.lee@deans.pharm.utah.edu
Koh
Jae Joon
JJ
Han
Sang-Oh
SO
Ko
Kyung Soo
KS
Ki
Sung Wan
SW
D000818:Animals; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000517:prevention & control*; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000235:genetics*; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010957:Plasmids / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012995:Solubility
D004337:Drug Carriers; C414262:poly((4-aminobutyl)glycolic acid); D015847:Interleukin-4; D011100:Polyglycolic Acid