Investigation of Lipid-based Drug Delivery Vehicle using Molecular Dynamics Simulations
ORAL
Abstract
Jun Xie1, M. Jayne Lawrence2 & Christian D. Lorenz1
1Department of Physics King’s College London
2Division of Pharmacy & Optometry, University of Manchester
jun.xie@kcl.ac.uk ; jayne.lawrence@manchester.ac.uk
Lipid-based drug carriers are an attractive option in the nanomedicines field for the delivery of various types of drugs nowadays. Previously we have shown that the digestion of short tail PC lipids (C6PC) by the PLA2 enzyme has a significant effect on the size, shape and stability of the resulting micelles [1]. However, previously there had been no investigations of the capability of this formulation as a drug delivery vehicle.
In this work, we have studied the interactions between micelles with compositions representing various degrees of digestion with a model ordered (70% DPPC & 30% Cholesterol) and a model disordered (100% DOPC) lipid membrane. Each of the different composition micelles were destabilised by interacting with the two different membrane systems. We found that as the micelles are digested (e.g. contain more of the digestion products (a C6 fatty acid (C6FA) and a lysolated C6 lipid (C6LYS)) as opposed to the original C6PC lipid they destabilise more rapidly. We find that the C6FA and C6PC molecules that dissociate from the micelle then insert into the membrane and have an effect on the structural properties of the membrane. In this presentation, I will present the interactions of the various constituent molecules with the two different lipid membranes and the effect that their insertion into the membrane has on the two different membranes. Additionally, I will report the dynamics of the molecules once they are inserted into the membrane. The findings presented provide insight into how the natural digestion of these micelles could result in them enhancing the delivery of encapsulated drugs by increasing the permeability of the membranes.
(1) Pink, D. L.; Foglia, F.; Barlow, D. J.; Lawrence, M. J.; Lorenz, C. D. Small 2021, 17, 2004761.
1Department of Physics King’s College London
2Division of Pharmacy & Optometry, University of Manchester
jun.xie@kcl.ac.uk ; jayne.lawrence@manchester.ac.uk
Lipid-based drug carriers are an attractive option in the nanomedicines field for the delivery of various types of drugs nowadays. Previously we have shown that the digestion of short tail PC lipids (C6PC) by the PLA2 enzyme has a significant effect on the size, shape and stability of the resulting micelles [1]. However, previously there had been no investigations of the capability of this formulation as a drug delivery vehicle.
In this work, we have studied the interactions between micelles with compositions representing various degrees of digestion with a model ordered (70% DPPC & 30% Cholesterol) and a model disordered (100% DOPC) lipid membrane. Each of the different composition micelles were destabilised by interacting with the two different membrane systems. We found that as the micelles are digested (e.g. contain more of the digestion products (a C6 fatty acid (C6FA) and a lysolated C6 lipid (C6LYS)) as opposed to the original C6PC lipid they destabilise more rapidly. We find that the C6FA and C6PC molecules that dissociate from the micelle then insert into the membrane and have an effect on the structural properties of the membrane. In this presentation, I will present the interactions of the various constituent molecules with the two different lipid membranes and the effect that their insertion into the membrane has on the two different membranes. Additionally, I will report the dynamics of the molecules once they are inserted into the membrane. The findings presented provide insight into how the natural digestion of these micelles could result in them enhancing the delivery of encapsulated drugs by increasing the permeability of the membranes.
(1) Pink, D. L.; Foglia, F.; Barlow, D. J.; Lawrence, M. J.; Lorenz, C. D. Small 2021, 17, 2004761.
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Presenters
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Jun Xie
King's College London
Authors
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Jun Xie
King's College London