Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury

Drug Delivery

Gui-Ling Song¹  Lian Yu¹  Xu-Qi Kang²  Shu-Juan Li²  Jian You²  Jing-Bo Hu²  Jing Qi²  Xiao-Ling Xu²  Xiao-Juan Wang²  Xiao-Ying Ying²  Yong-Zhong Du²  Jia-Hui Wu²  Fei-Yang Jin²  Di Liu² 

[1] Jiamusi University;Zhejiang University;

关键词: sialic acid;    nanoparticles;    e-selectin;    kidney targeting;    ischemia reperfusion;    acute kidney injury;   

DOI  :  10.1080/10717544.2017.1410258

来源: DOAJ

【 摘 要 】

In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the inflamed vascular endothelium. DXM-loaded SA-conjugated polyethylene glycol (PEG)ylated NPs (SA-NPs) are prepared via solvent diffusion method and show the good colloidal stability. SA-NPs reduce apoptotic human umbilical vein endothelial cells (HUVECs) via downregulating oxidative stress-induced Bax, upregulating Bcl-xL, and inhibiting Caspase-3 and Caspase-9 activation. Cellular uptake results suggest SA-NPs can be specifically internalized by the inflamed vascular endothelial cells (H2O2-pretreated HUVECs), and the mechanism is associated with the specific binding between SA and E-selectin receptor expressed on the inflamed vascular endothelial cells. Bio-distribution results further demonstrated the enhanced renal accumulation of DXM is achieved in AKI mice treated with SA-NPs, and its content is 2.70- and 5.88-fold higher than those treated with DXM and NPs at 6 h after intravenous administration, respectively. Pharmacodynamic studies demonstrate SA-NPs effectively ameliorate renal functions in AKI mice, as reflected by improved blood biochemical indexes, histopathological changes, oxidative stress levels and pro-inflammatory cytokines. Moreover, SA-NPs cause little negative effects on lymphocyte count and bone mineral density while DXM leads to severe osteoporosis. It is concluded that SA-NPs provide an efficient and targeted delivery of DXM for ischemia-reperfusion-induced injury-induced AKI, with improved therapeutic outcomes and reduced adverse effects.

【 授权许可】

Unknown