An anti-ROS/hepatic fibrosis drug delivery system based on salvianolic acid B loaded mesoporous silica nanoparticles.

The rhodamine B (RhB) covalently grafted SBA-15-structured mesoporous silica nanoparticles (MSNs-RhB) of high surface area (750 m(2) g(-1)), large pore volume (0.7 cm(3) g(-1)), uniform particle size (about 400 nm) and positively charged surface (29.6 +/- 5.0 mV), has been developed as a drug delivery system (SAB@MSNs-RhB) for anti-ROS (reactive oxygen species)/hepatic fibrosis by loading a negatively charged drug salvianolic acid B (SAB). The dosage formulation SAB@MSNs-RhB effectively protected the loaded drug SAB from decomposition. The multi-release experimental results showed that SAB@MSNs-RhB exhibited an outstanding SAB sustained-release property, and relatively high SAB release rates and concentrations in a long term after the consumption of previously released SAB as compared to SAB loaded MSNs (SAB@MSNs) of negatively charged surface (-31.1 +/- 2.6 mV). The influences of the drug concentration, incubation time, drug formula and drug carrier on the ROS level, proliferative activity and cytotoxicity of LX-2 cells were evaluated. The results showed that the inhibiting effect of SAB@MSNs-RhB on the ROS level and proliferative activity of LX-2 cells was more remarkable than free SAB in a long term (72 h), and became more intensive with the increase of the sample concentration and the incubation time. SAB@MSNs-RhB enhanced the cellular drug uptake, the drug bioaccessability and efficacy for anti-ROS/hepatic fibrosis via the nanoparticles-mediated endocytosis and the sustained release of the drug. There was no visible cytotoxicity of free SAB, MSNs-RhB and SAB@MSNs-RhB against LX-2 cells in a broad concentration range (0.5-100 microm) and incubation time periods up to 72 h. The blood compatibility of the carrier MSNs-RhB was evaluated by investigating the hemolysis and coagulation behaviors in a broad concentration range (50-500 microg mL(-1)) under in vitro conditions. The results suggested that MSNs-RhB possessed good blood compatibility. Copyright 2010 Elsevier Ltd. All rights reserved.