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

Area of Science:

• Pharmacology
• Materials Science
• Biophysics

Background:

• Drug interactions with phospholipid bilayers are crucial for cell membrane behavior and liposomal drug delivery.
• Liposomal drug delivery in ocular medicine offers a strategy to overcome eye barriers and enhance drug targeting.

Purpose of the Study:

• To characterize the interactions of difluprednate (DFP) and fluorometholone (FML) with phosphatidylcholine (PC) multilamellar vesicles.
• To understand how drug lipophilicity influences drug-lipid interactions in potential ocular delivery systems.

Main Methods:

• Solid-state ¹⁹F NMR spectroscopy to determine drug orientation within lipid bilayers.
• Raman spectroscopy to analyze drug-lipid separation in dried films.
• ³¹P NMR to confirm lipid bilayer integrity at high drug concentrations.

Main Results:

• ³¹P NMR confirmed lipid bilayer stability at a drug:lipid molar ratio of 1:10.
• ¹⁹F NMR indicated distinct average orientations for FML and DFP within the lipid bilayer.
• Raman spectra showed PC separating from the more lipophilic DFP but not from the less lipophilic FML.

Conclusions:

• DFP and FML exhibit different interaction behaviors with phosphatidylcholine bilayers, influenced by their lipophilicity.
• The findings provide insights into drug-lipid interactions relevant for designing improved ocular liposomal formulations.
• This study highlights the utility of combined NMR and Raman spectroscopy for characterizing drug delivery systems.