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Regular version of the site

Article

Behavior of Doxorubicin Lipophilic Conjugates in Liposomal Lipid Bilayers.

Russian Journal of Bioorganic Chemistry. 2018. Vol. 44. No. 6. P. 732-739.
Алексеева А. С., Волынский П. Е., Chugunov A., Онищенко Н. Р., Молотковский Ю. Г., Efremov R., Болдырев И. А., Водовозова Е. Л.

Preparation of liposomal formulations containing water-soluble drugs in the form of lipophilic
prodrugs in their lipid bilayer is of considerable interest. Previously, we synthesized doxorubicin dioleoyl
glyceride and oleoyl conjugates intended for incorporation into fluid-phase liposomal bilayers. In this work,
we studied the behavior of lipid conjugates in bilayers prepared from palmitoyl oleoyl phosphatidylcholine
and dimyristoyl phosphatidylcholine using methods of fluorescence spectroscopy and molecular modeling.
The conjugates were shown to have limited mobility in lipid bilayers, which can be explained by the formation
of hydrogen bonds between the doxorubicin aglycone and the lipid phosphate groups. In the liposome membrane,
lipophilic conjugates also tend to form clusters through interaction of doxorubicin moieties. Oleoyl
chains stretch in parallel to the acyl residues of phospholipids. Due to the formation of a larger number of
hydrogen bonds, the oleoyl conjugates interacted with the bilayer more effectively than the dioleoyl glyceride
counterparts. These properties of doxorubicin conjugates can affect both the possibility of their incorporation
into the lipid bilayer (from the therapeutic effect point of view) and intracellular release of the antibiotic drug
by means of enzymolysis.