Lipoic acid nanoforms based on phosphatidylcholine: production and characteristics.

We describe the dynamics of lipoic acid (LA) alone, incorporated in liposomes and as a part of nanoemulsions. Mass spectrometry shows that LA in water forms aggregates of two or three molecules in the form of a negatively charged ion and a neutral molecule. Phosphatidylcholine (PC)-based nanoforms of LA as liposomes and nanoemulsions with a particle size equal to 145 nm are characterized by a high degree of incorporation of LA into the nanoparticles and long-term stability during storage at room temperature. Dynamic light scattering (DLS) gives the polydispersity index of the nanoforms (> 0.3), characterizing the homogeneity of the obtained nanodispersions. We found that such emulsions can significantly (5 ×) increase the concentration of LA in the aqueous phase (5-7 mg/mL) when compared with an aqueous solution of LA (1 mg/mL) and by 40% when compared with PC liposomes (4 mg/mL). Moreover, the inclusion of LA in liposomes and nanoemulsions from PC did not change the neutral ζ-potential characteristic of PC nanoforms. CryoTEM established that the structural organization of the liposomes practically did not differ from nanoemulsions and both nanoforms contained both multilayer and single-layer vesicles. When studying the release kinetics of LA from phosphatidylcholine nanoforms, we found that at 22 h, 45-55% of LA was released from nanoparticles, but that at the initial stage of the process LA was slowly released from the nanoemulsions and rapidly from the liposomes. Conductance measurements indicate that LA delivered in all the three forms increase membrane permeability, though this result is most marked with the LA in PC liposomes.

[The study of the membrane-protective potential of the combination of 2-ethyl-6-methyl-3-hydroxypyridine-succinate and citicoline]. / Issledovanie membranoprotektivnogo potentsiala kombinatsii preparatov 2-étil-6-metil-3-oksipiridina-suktsinata i tsitikolina.

AIM: To assess the changes in the composition of plasma phospholipids in patients with chronic cerebrovascular disease treated with neuroprotectors 2-ethyl-6-methyl-3-hydroxypyridine succinate (neurox) and citicoline (neipilept), the natural metabolites involved in biochemical processes in the body, and their composition. MATERIAL AND METHODS: The study included 40 patients, 18 men and 22 women, aged from 54 to 72 years, with chronic cerebrovascular disease at the decompensation stage complicated with the hypertensive crisis and/or arrhythmia. RESULTS AND CONCLUSION: During extraction of phospholipids from blood cells, a significant decrease in the amount of total lipids was found to the end of treatment of patients who received neurox or neipilept or their combination. The study of quantitative composition of phospholipids showed no significant changes in patients treated with neurox, while the use of citicoline or combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate resulted in the increase of their total mass. There were no significant changes in the qualitative composition of phospholipid classes in blood plasma in patients treated with neurox. In patients treated with neipilept or with the combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate, plasma phosphatidylcholine was significantly increased. No significant changes in the content of phosphatidylinositol, phosphatidylserine and sphingomyelin were observed.

[Liposomal form of lipoic acid: preparation and determination of antiplatelet and antioxidant activity]. / Liposomal'naia forma lipoevoi kisloty: poluchenie i opredelenie antiagregatsionnoi i antioksidantnoi aktivnosti.

Optimal conditions for obtaining phosphatidylholine (PC) liposomes with lipoic acid (LA) are chosen that lead to the formation of nanoparticles with a size of 175¸284 nm with efficiency (extent) of inclusion of LA in liposomes equal 85% and characterized by a slow release of substance from the nanoparticles. The effect of "empty" liposomes and liposomal form of LA on platelet aggregation induced by arachidonic acid (AA) is established. It is found that liposomes with LА inhibit platelet aggregation, caused by AА, to 80%. In addition, it is shown that "empty" liposomes slightly (to 30%) suppress platelet aggregation, caused by AА. The amount of TBA-sensitive products in samples of platelet-rich plasma (PRP) incubated with liposomal LA is determined. It is shown that LA in the composition of liposomes retains its antioxidant properties, and the amount of products of lipid peroxidation in platelet-rich plasma decreases in a dose-dependent manner when arachidonic acid is used as an inductor of platelet aggregation. It is assumed that the antiplatelet action of the liposomal form of LА is induced by inhibition of the initiation of lipid peroxidation products caused by exogenous inducer AА. It is supposed that, after additional research, the liposomal form of LA can be considered as a new drug in complex treatment of cerebral ischemia.