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Sialic acid-modified dexamethasone lipid calcium phosphate gel core nanoparticles for target treatment of kidney injury

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Abstract

Acute kidney injury (AKI) is a common clinical disease with high morbidity and mortality. Glucocorticoids are drugs that effectively relieve AKI, but the systemic side effects of long-term use limit their use. Herein, we constructed sialic acid-modified dexamethasone sodium phosphate (Dsp)-loaded lipid calcium phosphate gel core nanoparticles (SA-NPs) for the targeted treatment of ischemia–reperfusion (I/R)-induced AKI to improve efficacy and reduce side effects. The obtained nanoparticles could effectively encapsulate Dsp with 66.8% encapsulation efficiency and 4.56% (w/w) drug content. In vitro release indicates that the nanoparticles have a certain sustained release effect and have the characteristics of acid-sensitive release. And SA-NPs significantly increased the cellular uptake and kidney accumulation respectively through the combination of SA and E-selectin receptors overexpressed in inflamed vascular endothelial cells. Besides, the in vivo pharmacokinetic studies showed that Dsp-loaded SA-NPs significantly increased the residence time in the body and their plasma half-life was 1.7 times that of free Dsp. SA-NPs significantly improved the renal function, decreased the level of pro-inflammatory factors, and adjusted the oxidative stress factors and apoptotic proteins compared to free Dsp solution in pharmacodynamic studies. Moreover, little negative effects on blood glucose and bone mineral density were observed. Our study might provide a new strategy for the safe and effective targeting treatment of AKI or other related inflammatory diseases.

Graphical abstract: Sialic acid-modified dexamethasone lipid calcium phosphate gel core nanoparticles for target treatment of kidney injury

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Supplementary files

Article information


Submitted
12 Apr 2020
Accepted
22 May 2020
First published
25 May 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

Sialic acid-modified dexamethasone lipid calcium phosphate gel core nanoparticles for target treatment of kidney injury

H. Liu, H. Zhang, N. Yin, Y. Zhang, J. Gou, T. Yin, H. He, H. Ding, Y. Zhang and X. Tang, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/D0BM00581A

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