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

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.

Molecular interactions and physico-chemical characterization of quercetin-loaded magnetoliposomes.

The bioflavonoid quercetin may prevent magnetoliposomes oxidation, preserving their stability. In this work, the interaction between quercetin and asolectin-based magnetoliposomes was investigated by monitoring the hydration degree, vibrational, rotational and translational mobility parameters of the system as well as its thermodynamic properties. The efficiency of the encapsulation of maghemite magnetic nanoparticles was detected by high resolution-continuum source flame atomic absorption spectrometry (HR-CS FAAS). The magnetic behavior of the system was studied by vibrating sample magnetometry (VSM) technique. The size and surface charge of magnetoliposomes were detected by dynamic light scattering (DLS) and zeta potential (ζ-potential) measurements. The influence of quercetin on the physico-chemical parameters of the magnetoliposomes was evaluated by Fourier transform infrared spectroscopy (FTIR), 31P and 1H nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. In vitro antioxidant and antitumoral assays were also performed for the magnetoliposomes. An insertion of quercetin into magnetoliposomes reduced the efficiency of the encapsulation of maghemite nanoparticles by 11%, suggesting a significant interaction between flavonoid and nanoparticles in a specific region of the system. Quercetin discreetly decreased the saturation magnetization of magnetoliposomes, but did not affect the superparamagnetic behavior of the system. 31P and 1H NMR results showed that quercetin did not alter the inverted hexagonal system phase state but decreased lipid polar head mobility. The flavonoid also seems to reorient the choline group above the bilayer phosphate membrane plane, as indicated by ζ-potential system values. FTIR, NMR and DSC responses showed that quercetin disordered the carbonyl and the methylene regions of the magnetoliposomes. Quercetin, as the nanoparticles, seems to be located in the polar head regions of magnetoliposomes, ordering it and diminishing the lipid intermolecular communication in the membrane carbonyl and non-polar regions. The lipid peroxidation of the magnetoliposomes was prevented 8-fold by the presence of quercetin in the system. Also, the flavonoid was responsible for a 45% reduction in the viability of glioma cells. Location and interactions between quercetin and magnetoliposomes components were discussed in order to be correlated with the results of biological activity, contributing to the design of more stable and efficient magnetoliposomes to be applied as contrast and antitumoral agents.