A.M. Butlerov Chemical Institute, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia.
Scientific and Educational Center of Pharmaceutics, Kazan Federal University, 420008 Kazan, Russia.
Int J Mol Sci. 2021 Jul 26;22(15):7950. doi: 10.3390/ijms22157950.
In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds are not used in targeted drug delivery systems due to their high affinity for cell membranes, both healthy and in cancer cells. Using the approach of creating supramolecular amphiphiles, we have developed self-assembling systems based on water-soluble pillar[5]arene and synthetic meroterpenoids containing geraniol, myrtenol, farnesol, and phytol fragments. The resulting systems can be used as universal drug delivery systems. It was shown by turbidimetry that the obtained pillar[5]arene/synthetic meroterpenoid systems do not interact with the model cell membrane at pH = 7.4, but the associates are destroyed at pH = 4.1. In this case, the synthetic meroterpenoid is incorporated into the lipid bilayer of the model membrane. The characteristics of supramolecular self-assembly, association constants and stoichiometry of the most stable pillar[5]arene/synthetic meroterpenoid complexes were established by UV-vis spectroscopy and dynamic light scattering (DLS). It was shown that supramolecular amphiphiles based on pillar[5]arene/synthetic meroterpenoid systems form monodisperse associates in a wide range of concentrations. The inclusion of the antitumor drug 5-fluoro-2'-deoxyuridine (floxuridine) into the structure of the supramolecular associate was demonstrated by DLS, 19F, 2D DOSY NMR spectroscopy.
近年来，由于其合成可用性、低毒性和生物相容性，梅罗萜类化合物在生物医学领域得到了广泛的应用。然而，由于它们与细胞膜（包括健康细胞和癌细胞）的高亲和力，这些化合物并未被用于靶向药物输送系统。我们采用了创建超分子两亲物的方法，开发了基于水溶性柱[5]芳烃和含有香叶醇、桃金娘醇、法呢醇和植醇片段的合成梅罗萜类化合物的自组装系统。所得系统可用作通用药物输送系统。浊度法表明，所得到的柱[5]芳烃/合成梅罗萜类化合物系统在 pH = 7.4 时与模型细胞膜不相互作用，但在 pH = 4.1 时会破坏配合物。在这种情况下，合成梅罗萜类化合物被掺入模型膜的脂质双层中。通过紫外-可见光谱和动态光散射（DLS）建立了超分子自组装、最稳定的柱[5]芳烃/合成梅罗萜类化合物配合物的结合常数和化学计量的特性。结果表明，基于柱[5]芳烃/合成梅罗萜类化合物系统的超分子两亲物在很宽的浓度范围内形成单分散配合物。通过 DLS、19F、2D DOSY NMR 光谱证明了抗肿瘤药物 5-氟-2'-脱氧尿苷（氟尿苷）被纳入超分子配合物的结构中。
