Synthesis and characterization of hyaluronic acid coated manganese dioxide microparticles that act as ROS scavengers

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial wall that leads to cardiovascular diseases which are the major cause of deaths worldwide. There is currently no treatment that can stop or reverse the disease. However, the use of microparticles with anti-inflammatory properties could represent a promising treatment. Herein, spherical microparticles with a core-shell structure and an average diameter of 1μm were synthesized. The microparticles were comprised of a MnCO3 and MnO2 core and a 4-arm PEG-amine cross-linked shell of hyaluronic acid. The HA-Mn-SM microparticles were loaded with D-α-tocopherol (vitamin-E) (TOC), to fabricate a targeted biocompatible delivery platform for the treatment of atherosclerotic inflamed cells. Loading and release studies of TOC demonstrated a lactic acid concentration dependant controlled release profile of the HA-Mn-SM mimicking the atherosclerotic environment where lactic acid is over-produced. The microparticles exhibited a high scavenging ability towards H2O2 in addition to the controlled generation of O2. The optimal results were obtained for 250μg/mL microparticles which in the presence of 1000μM H2O2 resulted in the scavenging of almost all the H2O2. Our results demonstrate that 50μg/mL of microparticles scavenged continuously produced H2O2 up to a concentration of 1000μM, a characteristic that demonstrates the sustained therapeutic effect of the HA-Mn-SM microparticles in an environment that mimics that of inflamed tissues. Our results indicate the potential use of HA-Mn-SM as a novel platform for the treatment of atherosclerosis. In vitro studies confirmed that the microparticles are not cytotoxic at concentrations up to 250μg/mL and for 72h. These preliminary results indicate the potential use of HA-Mn-SM as a novel drug delivery system for atherosclerotic tissues.