Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
Doctoral School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
Molecules. 2022 Feb 28;27(5):1589. doi: 10.3390/molecules27051589.
Cyclodextrins are high molecular weight, hydrophilic, cyclic, non-reducing oligosaccharides, applied as excipients for the improvement of the solubility and permeability of insoluble active pharmaceutical ingredients. On the other hand, beta-cyclodextrins are used as cholesterol sequestering agents in life sciences. Recently, we demonstrated the cellular internalization and intracellular effects of cyclodextrins on Caco-2 cells. In this study, we aimed to further investigate the endocytosis of (2-hydroxylpropyl)-beta-(HPBCD) and random methylated-beta-cyclodextrin (RAMEB) to test their cytotoxicity, NF-kappa B pathway induction, autophagy, and lysosome formation on HeLa cells. These derivatives were able to enter the cells; however, major differences were revealed in the inhibition of their endocytosis compared to Caco-2 cells. NF-kappa B p65 translocation was not detected in the cell nuclei after HPBCD or RAMEB pre-treatment and cyclodextrin treatment did not enhance the formation of autophagosomes. These cyclodextrin derivates were partially localized in lysosomes after internalization.
环糊精是高分子量、亲水性、环状、非还原性寡糖，用作改善难溶性活性药物成分的溶解度和渗透性的赋形剂。另一方面，β-环糊精在生命科学中用作胆固醇螯合剂。最近，我们证明了环糊精在 Caco-2 细胞中的细胞内化和细胞内作用。在这项研究中，我们旨在进一步研究（2-羟丙基）-β-（HPBCD）和随机甲基化-β-环糊精（RAMEB）的内吞作用，以测试它们对 HeLa 细胞的细胞毒性、NF-κB 途径诱导、自噬和溶酶体形成的影响。这些衍生物能够进入细胞；然而，与 Caco-2 细胞相比，它们的内吞作用的抑制存在显著差异。在 HPBCD 或 RAMEB 预处理和环糊精处理后，未检测到 NF-κB p65 向细胞核转位，并且环糊精处理不会增强自噬体的形成。这些环糊精衍生物在内化后部分定位于溶酶体中。
