The Preparation And Evaluation Of Lipid-coated Microbubbles For Therapy

BackgroundNoninvasive ultrasound ablation of tumor is desirable although there are many other invasive methods. Recently, microbubble (MB) enhanced ultrasound cavitation was found to have great potential in therapy because MB can act both as a drug carrier and a cavitation nucleus. MB enhanced cavitation can not only impact regional tissues permeability but also facilitate drug delivery as well.The anionic lipid microbubble with net negative surface charge is known to stick to endothelium and to retain in capillaries 10 times more than the neutral microbubble through C3b complement- mediated attachment to endothelium. In that case, the anionic microbubbles are closer to endothelium when the acoustic cavitation happens. This could lead to more severe endothelial injury or cavitation-related bioeffects. The study is designed to prepare the prothrombin complex conjugated anionic lipid microbubbles. The acoustic cavitation of this prothrombin binded anionic microbubbles could enhance endothelial injury, activate thrombolic cascade and result in massive thrombosis and blockage in tumor microvasculature. The purpose of this study is to find a noninvasive ultrasound ablation of tumor angiogenesis. So, the preparation of prothrombin conjugated lipid microbubbles is critical and necessary step.ObjectivesThe first step tried to increase the negative surface charge of microbubbles by using more negative charged lipid in the lipid formula. The next step was to assess the physiochemical properties of the MB, including: MB surface electrical potential, bubble concentration, size and distribution. The final attempt was to bind the MB with prothrombin complex concengtrate through electrostatic conjugation or Biotin-avidin Bridge binding methods, to evaluate the binding of the MB to prothrombin complex and the stability, and...