Understanding a macromolecule translocation & reservoir attachment mechanism: slow drug release to membranes
This proposal follows on from our recent FIGARO publication in ACS Macro Letters: "Key Factors Regulating the Mass Delivery of Macromolecules to Model Cell Membranes: Gravity and Electrostatics". The aim of the project is to tune the attachment of reservoirs of macromolecules in the form of lamellar aggregates to supported lipid bilayers for continuous diffusion and slow release. We have shown already that the orientation of the membrane is of great importance and a macromolecule translocation + aggregate attachment mechanism only occurs on membranes of sufficient charge. There are 3 aims of this experiment. [1] To determine the underlying nature of the mechanism in terms of kinetic vs. thermodynamic barriers. [2] To resolve the translocation mechanism in terms of clustering of charged lipid first in the outer leaflet as the macromolecule binds then in the inner leaflet after translocation. [3] To determine the factors which affect surface multilayer formation in this complex biophysical system. With these results we aim to write one more research paper of relevance to the drug delivery community and one technical paper of interest to the neutron community before the end of 2014.
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Richard A. Campbell; CARDENAS; SOTRES Javier and WATKINS Erik. (2014). Understanding a macromolecule translocation & reservoir attachment mechanism: slow drug release to membranes. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.9-13-542
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