We monitored adsorption of a non-steroidal anti-inflammatory drug (NSAID), indomethacin, to a supported lipid bilayer composed of phospholipids of varying lipid phase and head group charge. These experiments were conducted under physiologically-relevant drug concentrations and at a range of pH conditions. We monitored second harmonic generation (SHG) signal at the aqueous-bilayer interface to quantify the number of adsorbed drug molecules and determine the impact of lipid fluidity, alkyl chain length and head group charge. Twice as much indomethacin adsorbed to liquid crystalline-phase lipids compared to gel-phase lipids. At neutral pH, indomethacin is negatively-charged and adsorbs with a lower binding affinity to lipids containing negatively-charged lipid head groups compared to zwitterioinic lipids or lipids containing positively-charged head groups. We varied temperature in our experiments to determine the enthalpic and entropic contributions to the free energies of adsorption. These studies provide a molecular-level picture of how variations in cell membrane composition impact the adsorption of a representative NSAID. Studies of indomethacin release from supported lipid bilayers were also conducted in aqueous conditions and indicate that a phospholipid-coated drug delivery device containing indomethacin may be remotely triggered by changes in temperature.

Second harmonic generation studies of indomethacin adsorption to phospholipid membranes

253rd National Meeting (2017)

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