期刊
EUROPEAN POLYMER JOURNAL
卷 164, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.eurpolymj.2021.110982
关键词
Salvianolic acid; Oxidative stress; Dextran; Stimuli responsive carriers
资金
- Ministry of Science and Technology [MOST 109-2221-E-011-037]
In this study, a laponite hydrogel containing ROS-responsive dextran-based nanoparticles was developed as a carrier for salvianolic acid B (SAB) delivery. The system exhibited good biocompatibility and sustained drug release properties, and was able to scavenge ROS and rescue cells from oxidative damage.
Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the peripheral arterial disease (PAD). Salvianolic acid B (SAB) is a natural phenolic compound and possesses antioxidant properties. However, the poor bioavailability of hydrophilic SAB may limit its applications. Boronic ester-based nanoparticles (NPs) as ROS-responsive carriers can release drug rapidly and selectively at damaged tissue. Dextran, a polysaccharide, has been used to decrease the platelet aggregation in PAD patients. Laponite, a synthetic nanoclay, has been widely used in biomedical applications. In the study, the laponite hydrogels containing ROS-responsive dextran-based NPs was developed as a carrier for SAB delivery. The synthesis processes of boronic ester modified dextran (PHB-DEX) were characterized by Fourier transform infrared spectrophotometer and thermogravimetry analyzer. The PHB-DEX NP was-195.3 nm with spherical structure and could be hydrolyzed completely within 9 min under oxidative stress. Optimal concentration of SAB to treat HUVECs was-100 mu M. The results of scanning electron microscopy demonstrated that SAB-loaded NPs (SAB-NPs) were well dispersed in laponite hydrogels matrix. The rheological behaviors of laponite containing SAB-NPs (LNPs) showed the shear-thinning properties and increase of fluidity when removing shear stress. The LNPs with sustained drug release properties could scavenge ROS and rescue human umbilical vein endothelial cells from oxidative damage via decrease of the inflammatory level (TNF, IL-1 alpha, IL-1 beta, IL-6, and MMP-9) and apoptosis. The biocompatibility of the developed hydrogels has been demonstrated in-vivo. The results suggested that the developed LNPs might have potentials for PAD treatment.
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