Shear-thinning hydrogels containing reactive oxygen species-responsive nanoparticles for salvianolic acid B delivery to rescue oxidative damaged HUVECs

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 μM. 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-1α, IL-1β, 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.