Dataset Information

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

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 ¹⁹ F 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). ³¹ P NMR confirms that the lipid bilayer tolerates a high drug concentration (a drug: lipid molar ratio of 1 : 10). The ¹⁹ F 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.

SUBMITTER: Mapley B

PROVIDER: S-EPMC9297973 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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<sup>19</sup> F Solid-State NMR and Vibrational Raman Characterization of Corticosteroid Drug-Lipid Membrane Interactions.

Mapley Bethany B Townsend David D Griffin John J Ashton Lorna L Middleton David A DA

ChemPlusChem 20211102 11

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 <sup>19</sup> F solid-state NMR spectroscopy are used to characterise the interactions of two ocular corticosteroid drugs, difluprednate (DFP) and fluorometholone (FML), with multilamellar vesicles of phospha ...[more]

PMID: 34726840

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Project description:Nonlamellar lipid membranes are frequently induced by proteins that fuse, bend, and cut membranes. Understanding the mechanism of action of these proteins requires the elucidation of the membrane morphologies that they induce. While hexagonal phases and lamellar phases are readily identified by their characteristic solid-state NMR line shapes, bicontinuous lipid cubic phases are more difficult to discern, since the static NMR spectra of cubic-phase lipids consist of an isotropic (31)P or (2)H peak, indistinguishable from the spectra of isotropic membrane morphologies such as micelles and small vesicles. To date, small-angle X-ray scattering is the only method to identify bicontinuous lipid cubic phases. To explore unique NMR signatures of lipid cubic phases, we first describe the orientation distribution of lipid molecules in cubic phases and simulate the static (31)P chemical shift line shapes of oriented cubic-phase membranes in the limit of slow lateral diffusion. We then show that (31)P T2 relaxation times differ significantly between isotropic micelles and cubic-phase membranes: the latter exhibit 2 orders of magnitude shorter T2 relaxation times. These differences are explained by the different time scales of lipid lateral diffusion on the cubic-phase surface versus the time scales of micelle tumbling. Using this relaxation NMR approach, we investigated a DOPE membrane containing the transmembrane domain (TMD) of a viral fusion protein. The static (31)P spectrum of DOPE shows an isotropic peak, whose T2 relaxation times correspond to that of a cubic phase. Thus, the viral fusion protein TMD induces negative Gaussian curvature, which is an intrinsic characteristic of cubic phases, to the DOPE membrane. This curvature induction has important implications to the mechanism of virus-cell fusion. This study establishes a simple NMR diagnostic probe of lipid cubic phases, which is expected to be useful for studying many protein-induced membrane remodeling phenomena in biology.

Dataset Information

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

Publications

<sup>19</sup> F Solid-State NMR and Vibrational Raman Characterization of Corticosteroid Drug-Lipid Membrane Interactions.

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Dataset Information

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

Publications

<sup>19</sup> F Solid-State NMR and Vibrational Raman Characterization of Corticosteroid Drug-Lipid Membrane Interactions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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