Abstract
Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different fluorescent labeling on the same cyclodextrin derivative has not been studied. The consequences of the cellular internalization of cyclodextrins have not been revealed yet either. The aims of this study were to compare the cellular internalization of fluorescein- and rhodamine-labeled (2-hydroxypropyl)-, (HPBCD) and randommethyl-β-cyclodextrins (RAMEB) and to investigate the intracellular effects of these derivatives on Caco-2 cells. Stimulation of the NF-kappa B pathway and autophagy and localization of these derivatives in lysosomes were tested. The endocytosis of these derivatives was examined by fluorescence microscopy and flow cytometry. Both fluorescein- and rhodamine-labeled derivatives entered the cells, therefore the type of the fluorescent labeling did not influence their internalization. Cyclodextrin pretreatment did not activate the translocation of the p65 subunit of the NF-kappa B heterodimer into the cell nuclei from the cytoplasm. After HPBCD or RAMEB treatment, formation of the autophagosomes did not increase compared to the control sample and at the same time these derivatives could be detected in lysosomes after internalization.
Highlights
Cyclodextrins are extensively used materials in drug formulations to increase water solubility, to engineer new delivery systems and to modulate the bioavailability of lipophilic drugs
We reported the endocytosis of these molecules, but we have not compared the effect of different fluorescent labeling on the same cyclodextrin ring yet
We found that only 50 mM RAMEB treatment showed significant toxic effects compared to the control cells after 30 min (Figure 2B)
Summary
Cyclodextrins are extensively used materials in drug formulations to increase water solubility, to engineer new delivery systems and to modulate the bioavailability of lipophilic drugs. The pharmaceutical and the food industry use cyclodextrins to mask unpleasant flavors, reduce irritant effects or for stabilization [1,2,3]. These molecules were widely applied as active pharmaceutical ingredients and in biomedical technologies [4]. Pharmaceutics 2021, 13, 157 the late endosomes/lysosomes of Niemann Pick mutant cells [7]. This discovery led to the clinical application of HPBCD in the treatment of Niemann-Pick disease type C [8,9]
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