Studies of aqueous solutions of antipsychotic drugs clozapine and chlorpromazine adsorbed to supported lipid bilayers composed of phospholipids of varying lipid phase, head group charge and cholesterol content were conducted. The nonlinear optical method, second harmonic generation, was used to directly detect adsorbed drugs at the aqueous-lipid interface without any extrinsic tags. Binding affinities and the impact of lipid fluidity and electrostatic interactions were quantified. Temperatures were varied under biologically-relevant conditions and the relative enthalpic and entropic contributions to free energies of adsorption were found to vary based on lipid composition. These studies provide mechanistic insight into how drug structure impacts interactions with phospholipids to inform studies of lipid-based drug delivery materials.

Quantifying drug adsorption to lipid membranes using second harmonic generation

2019 Fall National Meeting

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