Development of Stealth Polymeric Ultrasound Contrast Agents

Abstract

Previous research in our lab has shown that when injected intravenously, drug-loaded polymeric ultrasound contrast agents (UCAs) accumulate within the liver and spleen likely caused by recognition of the UCA by the complement proteins within the blood and uptake by the mononuclear phagocyte system. This study investigates two means of incorporating polyethylene glycol (PEG), a well-researched molecule used for immune system avoidance, into the shell of UCAs to facilitate avoidance mechanisms. The first route used a PEG-polylactic acid (PLA) copolymer to create the UCAs via a water-oil-water emulsion technique. A second approach used d-α tocopheryl polyethylene glycol 1000 succinate (TPGS) as a surfactant during the creation of UCAs with PLA. The resulting formulations of pegylated UCAs were compared to control UCAs created from PLA and a surfactant solution of polyvinyl alcohol (PVA). The impact of adding PEG on size, surface charge, surface morphology, acoustic enhancement, and UCA stability was determined under simulated body conditions. It was seen that complete replacement of PLA with PEG-PLA or PVA with TPGS did not result in functional UCAs. However, PEG could be added by both means in conjunction with PLA and PVA to create UCAs with minimal changes to properties.