Licofelone-DPPC Interactions: Putting Membrane Lipids on the Radar of Drug Development

(1) : Membrane lipids have been disregarded in drug development throughout the years. Recently, they gained attention in drug design as targets, but they are still disregarded in the latter stages. Thus, this study aims to highlight the relevance of considering membrane lipids in the preclinical pha...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-01, Vol.24 (3), p.516
Main Authors: Pereira-Leite, Catarina, Lopes-de-Campos, Daniela, Fontaine, Philippe, Cuccovia, Iolanda M, Nunes, Cláudia, Reis, Salette
Format: Article
Language:English
Subjects:
Absorption spectroscopy
Anti-inflammatory agents
BAM
Brewster angle
DPPC
Drug development
GIXD
Infrared reflection
Infrared spectroscopy
Isotherms
langmuir isotherms
Lecithin
licofelone
lipid monolayers
Lipids
Membranes
Microscopy
Morphology
Nonsteroidal anti-inflammatory drugs
Packing density
Pharmacokinetics
Pharmacology
Phase transitions
Phosphatidylcholine
Phosphocholine
PM-IRRAS
Proteins
Signal transduction
Toxicity
X-ray diffraction
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Summary:(1) : Membrane lipids have been disregarded in drug development throughout the years. Recently, they gained attention in drug design as targets, but they are still disregarded in the latter stages. Thus, this study aims to highlight the relevance of considering membrane lipids in the preclinical phase of drug development. (2) : The interactions of a drug candidate for clinical use (licofelone) with a membrane model system made of 1,2-dipalmitoyl- -glycero-3-phosphocholine (DPPC) were evaluated by combining Langmuir isotherms, Brewster angle microscopy (BAM), polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and grazing-incidence X-ray diffraction (GIXD) measurements. (3) : Licofelone caused the expansion of the DPPC isotherm without changing the lipid phase transition profile. Moreover, licofelone induced the reduction of DPPC packing density, while increasing the local order of the DPPC acyl chains. (4) : The licofelone-induced alterations in the structural organization of phosphatidylcholine monolayers may be related to its pharmacological actions. Thus, the combination of studying drug-membrane interactions with the pharmacological characterization that occurs in the preclinical stage may gather additional information about the mechanisms of action and toxicity of drug candidates. Ultimately, the addition of this innovative step shall improve the success rate of drug development.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24030516