Synthesis, self-assembly and functional activity of a new pyrrolidinium surfactant conjugated with lipoic acid

The work is devoted to the synthesis, study of self-assembly and functional activity of novel amphiphiles based on a conjugate of pyrrolidinium fragment and lipoic acid (LPS-n, where n = 10, 12, 14, 16). It was shown by tensiometry, conductometry, and fluorescence spectroscopy, that embedding the lipoic acid fragment reduced the critical micelle concentration of the pyrrolidinium surfactants by up to 15 times compared to their analogues functionalized with hydroxyethyl group. The amphiphiles exhibit high solubilizing capacity toward poorly soluble drugs, including nonsteroidal anti-inflammatory (indomethacin and naproxen) and antidiabetic (glipizide) medicines. The formation of large, spherical vesicles with a diameter of up to 250 nm was established, depending on the alkyl chain length. The bactericidal activity of amphiphiles against E. faecalis and S. aureus (including methicillin-resistant MRSA-2 strain) was 3–6 times higher compared with norfloxacin. The anticancer activity of LPS-16 (IC50=5.6 µM) against duodenal adenocarcinoma cells HuTu 80 was at the level of 5-fluorouracil (IC50=5 µM) with a selectivity index of 4.6.