Understanding Structure and Stability for The Development of Novel Artificial Oxygen Carriers

Red blood cell concentrates (RBC) are an indispensable tool in various clinical scenarios; however, the available quantity is already highly limited, which will become an even more severe problem in the future. To overcome these peculiarities and limitations of RBCs, we developed albumin-derived perfluorocarbon-based artificial oxygen carriers (A-AOCs), that are comprised of a perfluorodecalin (PFD) nano-emulsion core and an albumin shell, and have already successfully supplied oxygen in extra-corporally perfused hearts and various animal models <b>[1]</b>.<br/><br/>The structure and stability of A-AOCs is sensitive to changes of the carrier solution, so we need to learn more about the structure and structural changes on the nanoscale. Conventional characterization techniques lack the spatial resolution (<i>e.g.</i> light scattering) or need dried and consequently non-physiological samples (<i>e.g.</i> SEM, TEM), and thus yield limited information on A-AOC structure in solution. We therefore use X-ray scattering techniques to study A-AOCs, which do not have such limitations and allow also to study dense, opaque suspensions.<br/><br/>In this contribution, we present recent results of X-ray scattering measurements on A-AOCs covering a wide, clinical-relevant concentration and temperature range. We investigate A-AOCs from different synthesis approaches, using ultra-sound <b>[2]</b> and microfluidizing techniques, which reveal different sizes and stabilities. Based on these findings, it is now possible to optimize the synthesis parameters, in order to yield stable A-AOCs of desired size and dispersity.<br/><br/>This study demonstrates the huge potential of X-ray scattering for the study of pharmaceutical and medical-relevant samples <b>[3]</b>, with direct implications for the development of new formulations.<br/><br/><br/><b>References:</b><br/><b>[1]</b> J. Jägers, A. Wrobeln, K. B. Ferenz, <i>Pflugers. Arch.</i> <b>473</b>, 139 (2021).<br/><b>[2]</b> A. Wrobeln, J. Laudien, C. Gross-Heitfeld, J. Linders, C. Mayer, B. Wilde, T. Knoll, D. Naglav, M. Kirsch, K. B. Ferenz, <i>Eur. J. Pharm. Biopharm. </i><b>115</b>, 52 (2017).<br/><b>[3]</b> S. S. Nogueira, A. Schlegel, K. Maxeiner, B. Weber, M. Barz, M. A. Schroer, C. E. Blanchet, D. I. Svergun, S. Ramishetti, D. Peer, P. Langguth, U. Sahin, H. Haas, <i>ACS Appl. Nano Mater.</i> <b>3</b>, 1063 (2020).