Dexamethasone-conjugated polyethylenimine as an effcient gene delivery carrier with anti-inflammatory effect for gene therapy of acute lung injury

초록

Dexamethasone is a potent synthetic member of the glucocorticoid steroid. IN this study, dexamethasone conjugated low molecular polyethylenimie (2 kDa, PEI-Dexa) was synthesized. PEI-Dexa/pbeta-Luc or PEI2K/pbeta-Luc complexes were tansfected into LPS stimulated RAW 264.7 cells and ELISA was perforemed to measure the levels of TNF-alpha and IL-6. PEI-Dexa transfected cells secreted less amount of inflammaotry cytokines compared to LPS induced control cells. However, PEI2K/pbeta-Luc omplexes tansfected cells did not show this effect. Then, EI-Dexa was characterized as a gene carrier. PEI-Dexa had transfection effciency comparable to PEI25K. MTT assays showed that PEI-Dexa has lower toxicity than PEI25K. For in vivo study, PEI-Dexa, PEI2K and PEI25K/pbeta-Luc compelxes were administrated into the BALB/c mice lungs by intratracheal injection. PEI-Dexa had higher gene delivery efficiency to the mouse lung than PEI2K or PEI25K. Finally, in vivo anti-inflammatory effect of PEI-Dexa was evaluated. ALI was induced by intratracheal administration of LPS in mice. The polymer/DNA complexes were administered to mouse and the level of TNF-alpha and IL-6 were determined in the BALF and tissues. The results indicated that PEI-Dexa reduced the inflammation in the LPS induced ALI.