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    Glycerol Solvates DPPC Headgroups and Localizes in the Interfacial Regions of Model Pulmonary Interfaces Altering Bilayer Structure

    Year: 2018

    Journal: Langmuir, Volume 34, JUN 12, page 6941–6954

    Authors: Terakosolphan, Wachirun; Trick, Jemma L.; Royall, Paul G.; Rogers, Sarah E.; Lamberti, Olimpia; Lorenz, Christian D.; Forbes, Ben; Harveylle, Richard D.

    Organizations: Office of Science and Technology through the EPSRC High End Computing Programme [EP/L000202]; Red Espanola de Supercomputacion; Government Pharmaceutical Organization of Thailand

    The inclusion of glycerol in formulations for pulmonary drug delivery may affect the bioavailability of inhaled steroids by retarding their transport across the lung epithelium. The aim of this study was to evaluate whether the molecular interactions of glycerol with model pulmonary interfaces provide a biophysical basis for glycerol modifying inhaled drug transport. Dipalmitoylphosphatidylcholine (DPPC) monolayers and liposomes were used as model pulmonary interfaces, in order to examine the effects of bulk glycerol (0-30% w/w) on their structures and dynamics using complementary biophysical measurements and molecular dynamics (MD) simulations. Glycerol was found to preferentially interact with the carbonyl groups in the interfacial region of DPPC and with phosphate and choline in the headgroup, thus causing an increase in the size of the headgroup solvation shell, as evidenced by an expansion of DPPC monolayers (molecular area increased from 52 to 68 angstrom(2)) and bilayers seen in both Langmuir isotherms and MD simulations. Both small angle neutron scattering and MD simulations indicated a reduction in gel phase DPPC bilayer thickness by similar to 3 angstrom in 30% w/w glycerol, a phenomenon consistent with the observation from FTIR data, that glycerol caused the lipid headgroup to remain oriented parallel to the membrane plane in contrast to its more perpendicular conformation adopted in pure water. Furthermore, FTIR measurements suggested that the terminal methyl groups of the DPPC acyl chains were constrained in the presence of glycerol. This observation is supported by MD simulations, which predict bridging between adjacent DPPC headgroups by glycerol as a possible source of its putative membrane stiffening effect. Collectively, these data indicate that glycerol preferentially solvates DPPC headgroups and localizes in specific areas of the interfacial region, resulting in structural changes to DPPC bilayers which may influence cell permeability to drugs.
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