RGD-peptides modifying dexamethasone: to enhance the anti-inflammatory efficacy and limit the risk of osteoporosis

Abstract

Dexamethasone (Dex) is one of the most effective anti-inflammatory glucocorticoids, while the side effect, osteoporosis seriously limits its clinical use. Cell adhesion is involved in the onset of inflammation and osteoporosis, and RGD-peptides are well known as anti-adhesion peptides. To enhance the anti-inflammatory efficacy and limit the osteoporotic risk of Dex three novel conjugates of RGDV, RGDS and RGDF covalently modified Dex are presented here. For the xylene-induced ear edema model the ear edema of the mice treated with the conjugates was significantly lower than that of the mice treated with Dex. Receiving 15 day therapy the total volumetric bonemineral density, the peripheral quantitative CT and the femur weight of the mice treated with the conjugates were significantly higher than those of the mice treated with Dex. Therefore covalently modifying Dex with RGDV, RGDS and RGDF not only increased the anti-inflammatory activity but also decreased the osteoporotic risk of Dex. In addition, the enhanced anti-inflammatory activity was correlated with the down-regulated DNA expression of the conjugates.