Hydration associated with drug release in albumin-based non-covalent drug delivery systems
The natural transport function, multiple ligand binding sites, and cellular interactions provide a rationale for the exploitation of albumin for drug delivery. But, at the same time, albumin ability to bind between 5000 to 43000 of water molecules, to help regulate the blood pressure, poses the question of the role of water displacement during ligand/drug binding and release to and from albumin. The present proposal aims to elucidate how changes in albumin hydration affect two model drugs (the highly specific warfarin and the non-specific Evans blue dye) release. Here, we focus on an osmotic stress method using small solutes (PEG200, 400, and 600) to affect albumin's structure and binding/release capacity. We will also utilize the state-of-the-art 'NUrF' set-up comprising a continuous flow-through cell, enabling a wide range of mixture compositions to be delivered by automatic mixing using an HPLC pump; combined with in situ UV/Vis absorption and fluorescence spectroscopies, and an inline density meter. The enhanced information will provide new structural insights to drive the design of drugs with improved binding and release profiles.
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DICKO Cedric; Judith E. Houston; JACKSON Andrew; Gudrun Lotze; MARTEL Anne; PORCAR Lionel; RENNIE Adrian R. and Andrea Scotti. (2021). Hydration associated with drug release in albumin-based non-covalent drug delivery systems. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.9-13-947
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