Interactions of dihydrochloride fluphenazine with DPPC liposomes: ATR-IR and 31P NMR studies.
The influence of dihydrochloride fluphenazine (FPh) on the dipalmitoylphosphatidylcholine (DPPC) bilayer structure was investigated using ATR-IR and (31)P NMR methods. The ATR-IR results indicate an increase in conformational disorder in the hydrophobic part compared with pure DPPC liposomes and a decrease in temperature of the chain-melting phase transition in FPh/DPPC liposomes. These effects depended on the concentration of the drug in the DPPC bilayer. The dihydrochloride fluphenazine molecules form H-bonds with the proton-acceptor carbonyl groups of DPPC molecules. At a higher concentration of the drug, the lipid bilayer structure is destroyed, and an isotropic phase is observed using (31)P NMR spectroscopy. The interactions between FPh and the lipid bilayer have a crucial role in MDR (multidrug-resistant) activity of this drug. These results improve one possible strategy of cancer chemoprevention with FPh accompanied by fluidization and destabilization of the model lipid bilayer structure.
Cieślik-Boczula
Katarzyna
K
Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw, Poland. kasia_cieslik0@yahoo.com
Szwed
Joanna
J
Jaszczyszyn
Agata
A
Gasiorowski
Kazimierz
K
Koll
Aleksander
A
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D014150:Antipsychotic Agents / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D005476:Fluphenazine / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013055:Spectrophotometry, Infrared; D013696:Temperature
D014150:Antipsychotic Agents; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D005476:Fluphenazine