Journal article
Partitioning of homologous nicotinic acid ester prodrugs (nicotinates) into dipalmitoylphosphatidylcholine (DPPC) membrane bilayers
Colloids and surfaces, B, Biointerfaces, Vol.78(1), pp.75-84
2010
DOI: 10.1016/j.colsurfb.2010.02.015
PMCID: PMC2873030
PMID: 20227859
Abstract
The partitioning behavior of a series of perhydrocarbon nicotinic acid esters (nicotinates) between aqueous solution and dipalmitoylphosphatidylcholine (DPPC) membrane bilayers is investigated as a function of increasing alkyl chain length. The hydrocarbon nicotinates represent putative prodrugs, derivatives of the polar drug nicotinic acid, whose functionalization provides the hydrophobic character necessary for pulmonary delivery in a hydrophobic, fluorocarbon solvent, such as perfluorooctyl bromide. Independent techniques of differential scanning calorimetry and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence anisotropy measurements are used to analyze the thermotropic phase behavior and lipid bilayer fluidity as a function of nicotinate concentration. At increasing concentrations of nicotinates over the DPPC mole fraction range examined (
X
DPPC
=
0.6–1.0), all the nicotinates (ethyl (C2H5); butyl (C4H9); hexyl (C6H13); and octyl (C8H17)) partition into the lipid bilayer at sufficient levels to eliminate the pretransition, and decrease and broaden the gel to fluid phase transition temperature. The concentration at which these effects occur is chain length-dependent; the shortest chain nicotinate, C2H5, elicits the least dramatic response. Similarly, the DPH anisotropy results demonstrate an alteration of the bilayer organization in the liposomes as a consequence of the chain length-dependent partitioning of the nicotinates into DPPC bilayers. The membrane partition coefficients (logarithm values), determined from the depressed bilayer phase transition temperatures, increase from 2.18 for C2H5 to 5.25 for C8H17. The DPPC membrane/water partitioning of the perhydrocarbon nicotinate series correlates with trends in the octanol/water partitioning of these solutes, suggesting that their incorporation into the bilayer is driven by increasing hydrophobicity.
Details
- Title: Subtitle
- Partitioning of homologous nicotinic acid ester prodrugs (nicotinates) into dipalmitoylphosphatidylcholine (DPPC) membrane bilayers
- Creators
- Vivian Ojogun - Department of Chemical and Materials Engineering, 177 Anderson Hall, University of Kentucky, Lexington, KY 40506-0046, United StatesSandhya M Vyas - Department of Occupational and Environmental Health, 100 Oakdale Campus, #124 IREH, University of Iowa, Iowa City, IA 52242-5000, United StatesHans-Joachim Lehmler - Department of Occupational and Environmental Health, 100 Oakdale Campus, #124 IREH, University of Iowa, Iowa City, IA 52242-5000, United StatesBarbara L Knutson - Department of Chemical and Materials Engineering, 177 Anderson Hall, University of Kentucky, Lexington, KY 40506-0046, United States
- Resource Type
- Journal article
- Publication Details
- Colloids and surfaces, B, Biointerfaces, Vol.78(1), pp.75-84
- DOI
- 10.1016/j.colsurfb.2010.02.015
- PMID
- 20227859
- PMCID
- PMC2873030
- NLM abbreviation
- Colloids Surf B Biointerfaces
- ISSN
- 0927-7765
- eISSN
- 1873-4367
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 2010
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute
- Record Identifier
- 9984001078902771
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