Dimiristoylphosphatidylcholine/genistein molecular interactions: A physico-chemical approach to anti-glioma drug delivery systems

• Published in: Chemistry and physics of lipids 2019-12, Vol.225, p.104828, Article 104828
• Main Authors: de Azambuja Borges, Carla Roberta Lopes, Silva, Nichole Osti, Rodrigues, Marisa Raquel, Germani Marinho, Marcelo Augusto, de Oliveira, Franciele Saes, Cassiana, Mendes, Horn, Ana Paula, Parize, Alexandre Luís, Flores, Darlene Correia, Clementin, Rosilene Maria, de Lima, Vânia Rodrigues
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Dimiristoylphosphatidylcholine; Genistein; Liposomes; Trans-gauche isomerization
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2019.104828

[Display omitted] •Genistein effect in dimyristoylphosphatidylcholine (DMPC) liposomes was studied.•Antioxidant and anti-glioma properties of the system were also investigated.•Genistein restricted the motion of polar and non-polar DMPC regions.•Liposome encapsulation increased genistein antioxidant activity in around 12%.•Liposome containing genistein 100 μM reduced glioma viability by approximately 80%. Regarding free genistein small delivery to the central nervous system, physico-chemical parameters of dimiristoylphosphatidylcholine liposome-loaded genistein were investigated, as well as its in vitro activity against the DPPH radical and glioma cells. Data obtained by UV–vis spectroscopy, Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, Differential Scanning Calorimetry and Dynamic Light Scattering were used to characterize the liposomal system with respect to motion restriction, hydration degree, trans-gauche isomerization and phase state. In vitro antitumoral effects were monitored through conting and viability assays. Genistein hydroxyl group and lipid hydrogen bonds may have important role in dimiristoylphosphatidylcholine phosphate and choline motion restriction. Genistein-induced choline restriction may be also related to a decrease in the group rotation rate. Genistein: dimiristoylphosphatidylcholine system showed higher molecular package at the acyl chains region compaired to empty liposomes, and it may be related to a decrease in gauche bonds quantity and system size. Lipid acyl chain length seems to influence different genistein effects on membranes, due to the presence of gauche conformers. Genistein: dimiristoylphosphatidylcholine liposome was more efficient as DPPH reducting system than the free-Gen. Liposomal system, at genistein 100 μM, was so efficient as the correspondent free-form genistein, probably showing higher stability to cross the blood-brain barrier. Genistein and the lipid did not show an additive activity against glioma cells. Antioxidant and anti-glioma genistein-loaded liposome potential may be related to the isoflavone location and its restriction effect in the lipid molecular motion. Anti-glioma activity may also be related to a decrease of system size and trans-gauche isomerization.