Glycerol solvates DPPC headgroups and localises in the interfacial regions of model pulmonary interfaces altering bilayer structure
| Autor: | Wachirun Terakosolphan, Jemma L. Trick, Ben Forbes, Sarah E. Rogers, Christian D. Lorenz, Olimpia Lamberti, Paul G. Royall, Richard D. Harvey |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Glycerol 1 2-Dipalmitoylphosphatidylcholine Lipid Bilayers Molecular Conformation 02 engineering and technology Molecular Dynamics Simulation 03 medical and health sciences chemistry.chemical_compound Molecular dynamics Monolayer Administration Inhalation Scattering Small Angle Electrochemistry General Materials Science Lung Spectroscopy Liposome Chemistry Bilayer technology industry and agriculture Surfaces and Interfaces 021001 nanoscience & nanotechnology Condensed Matter Physics 030104 developmental biology Solvation shell Dipalmitoylphosphatidylcholine Drug delivery Biophysics lipids (amino acids peptides and proteins) 0210 nano-technology |
| Zdroj: | Terakosolphan, W, Trick, J L, Royall, P G, Rogers, S E, Lamberti, O, Lorenz, C D, Forbes, B & Harvey, R D 2018, ' Glycerol solvates DPPC headgroups and localises in the interfacial regions of model pulmonary interfaces altering bilayer structure ', LANGMUIR . https://doi.org/10.1021/acs.langmuir.8b00866 |
| DOI: | 10.1021/acs.langmuir.8b00866 |
| Popis: | 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 Å2) and bilayers seen in both Langmuir isotherms and MD simulations. Both SANS and MD simulations indicated a reduction in gel phase DPPC bilayer thickness by ~3 Å 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 localises in specific areas of the interfacial region, resulting in structural changes to DPPC bilayers which may influence cell permeability to drugs. |
| Databáze: | OpenAIRE |
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