19F Solid-State NMR and Vibrational Raman Characterization of Corticosteroid Drug-Lipid Membrane Interactions

Mapley, Bethany and Townsend, David and Griffin, John and Ashton, Lorna and Middleton, David (2021) 19F Solid-State NMR and Vibrational Raman Characterization of Corticosteroid Drug-Lipid Membrane Interactions. ChemPlusChem, 86 (11). pp. 1517-1523. ISSN 2192-6506

Text (Manuscript)
Manuscript.pdf - Accepted Version
Available under License Creative Commons Attribution.
Download (732kB)

Abstract

Drug interactions with phospholipid bilayers underpin their behaviour in cell membranes and in liposomal delivery formulations. Liposomal drug delivery in ocular medicine can overcome the physical barriers of the eye and better enable the active molecule to reach its target. Here, Raman and 19F solid-state NMR spectroscopy are used to characterise the interactions of two ocular corticosteroid drugs, difluprednate (DFP) and fluorometholone (FML), with multilamellar vesicles of phosphatidylcholine (PC). 31P NMR confirms that the lipid bilayer tolerates a high drug concentration (a drug: lipid molar ratio of 1 : 10). The 19F NMR spectra of the drugs in lipid bilayers reveal that FML and DFP have different average orientations within the lipid bilayer. Raman spectra of dried lipid films reveal that PC separates from DFP but not from FML, the less lipophilic of the two drugs. This combined approach will assist the design of, and inform the development of, improved liposomal preparations.