Evaluation of the cytotoxicity of cyclodextrins and hydroxypropylated derivatives

Leroy-Lechat, Frédérique; Wouessidjewe, Denis; Andreux, J.‐P.; Puisieux, F.; Duchêne, Dominique

doi:10.1016/0378-5173(94)90080-9

Cited by 85 publications

(51 citation statements)

References 14 publications

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“…Ohtani et al (1989) reported that CDs induce hemolysis of human erythrocytes in the order ␤-Ͼ ␣-Ͼ ␥-CD. Leroy-Lechat et al (1994) also reported the same order of cytotoxicity of CDs toward P388 murine leukemic cells. No jpet.aspetjournals.org toxic effect toward Caco-2 cells has been observed for ␤-and ␥-CD (at 15 and 150 mM, respectively), whereas ␣-CD started to decrease the viability of Caco-2 cells at 25 mM (Ono et al, 2001).…”

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confidence: 52%

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Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Monnaert¹,

Tilloy²,

Bricout³

et al. 2004

J Pharmacol Exp Ther

100

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Cyclodextrins (CDs) can be envisaged to cure some diseases related to the brain, but the behavior of these compounds toward the blood-brain barrier (BBB) remains largely unexplored to envisage such clinical applications. To fulfill this gap, the toxicity and endothelial permeability for native, methylated, and hydroxypropylated ␣-, ␤-, and ␥-CDs have been studied on an in vitro model of BBB. As shown by the endothelial permeability for sucrose and immunofluorescence stainings, the native CDs are the most toxic CDs (␣-Ͼ ␤-Ͼ ␥-CD). Whereas the chemical modification of ␤-CD did not affect the toxicity of this CD, differences are observed for the ␣-and ␥-CD. To determine the origin of toxicity, lipid effluxes on the brain capillary endothelial cells were performed in the presence of native CDs. It was found that ␣-CD removed phospholipids and that ␤-CD extracted phospholipids and cholesterol. ␥-CD was less lipidselective than the other CDs. Finally, the endothelial permeability of each CD has been determined. Surprisingly, no structure/ permeability relationship has been observed according to the nature and chemical modifications of CDs.Cyclodextrins (CDs) are cyclic oligosaccharides composed of 6, 7, or 8 glucose units named ␣-, ␤-, or ␥-cyclodextrin, respectively. These compounds are widely used in the pharmaceutical field to improve the dissolution rate,

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confidence: 52%

“…Finally, only the hydroxypropylation decreased the toxicity by a factor of two for the ␥-CD. Leroy-Lechat et al (1994) have also described a marked reduced toxicity for HP-␥-CD compared with ␥-CD toward P388 murine leukemic cells. …”

Section: Discussionmentioning

confidence: 99%

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Monnaert¹,

Tilloy²,

Bricout³

et al. 2004

J Pharmacol Exp Ther

100

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“…Leroy-Lechat et al 11) also reported the same order of cytotoxicity of CyDs toward P388 murine leukaemic cells as that of hemolysis. Our preliminary data indicated that the cytotoxicity of CyDs toward RAW264.7 cells, a mouse macrophage-like cell line, increased in the order of g-Ͻa-Ͻb-CyD.…”

Section: Resultsmentioning

confidence: 55%

A Moderate Interaction of Maltosyl-α-cyclodextrin with Caco-2 Cells in Comparison with the Parent Cyclodextrin

Ono

Arima

Hirayama

et al. 2001

Biological & Pharmaceutical Bulletin

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The natural cyclodextrins (CyDs) and the chemically modified hydrophilic CyDs have been extensively used to improve solubility, stability and bioavailability of various insoluble drugs in water. [1][2][3] Among the chemically modified hydrophilic CyDs, oral preparations and parenteral injections containing high amounts of 2-hydroxypropyl-b-cyclodextrin (HP-b-CyD) have been commercialized in the United States and in some parts of Europe. In addition, the pharmaceutical preparations containing sulfobutyl ether-b-CyD (SBE-bCyD) have been hopefully developing. Branched CyDs have some superior characteristics to the parent CyDs and the amorphous CyDs such as HP-b-CyD and SBE-b-CyD: high purity, excellent solubility in water and organic solvents, and lower surface activity. [4][5][6] Another advantage of branched CyDs is a relatively low local irritancy: the hemolytic activity of branched CyDs is lower than those of the parent CyDs, and the leakage of intestinal constituents induced by gluco-4-7) On account of these beneficial properties, branched CyDs are recently expected for pharmaceutical use. However, there is no paper evaluating the cytotoxicity of branched CyDs on gastrointestinal epithelial cells.Caco-2 cells, a human colon adenocarcinoma cell line, have been shown to be a valuable in vitro model of intestinal mucosa. To date, there are a number of studies regarding the passive and active transport of various drugs and cytotoxicity of drugs and absorption enhancers. However, the interactions of branched CyDs such as maltosyl-a-CyD (G 2 -a-CyD) and G 2 -b-CyD with Caco-2 cell monolayers are still unclear, although there are two reports as to the cytotoxicity of DM-bCyD, HP-b-CyD and SBE-b-CyD toward Caco-2 cell monolayers. 8,9) In the present study, the effects of G 2 -a-CyD and G 2 -bCyD on human intestinal epithelial cells were studied using Caco-2 cells and compared with those of natural CyDs (a-, b-and g-CyD) for the following points: 1) viability of the cells, 2) transepithelial electrical resistance (TEER) in the cell monolayers, 3) the apical-to-basolateral (AP-to-BL) or basolateral-to-apical (BL-to-AP) transport of mannitol and rhodamine 123, which are paracellular and transcellular transport markers, respectively, across the monolayers, and 4) the release of biological membrane components such as proteins and phospholipids from the cells into the apical side. To elucidate the difference in the interaction with phospholipids between G 2 -a-CyD or a-CyD, the changes in surface tension of L-a -dipalmitoylphosphatidylcholine (DPPC) monolayers formed onto water by adding G 2 -a-CyD or a-CyD were evaluated. MATERIALS AND METHODSMaterials a-, b-and g-CyDs were donated by Nihon Shokuhin Kako (Tokyo, Japan). G 2 -a-CyD and G 2 -b-CyD were obtained from Bio Research Corporation of Yokohama (Yokohama, Japan). Tween 20 was purchased from Nacalai Tesque (Kyoto, Japan). Fetal calf serum (FCS) was purchased from Nichirei (Tokyo, Japan). Dulbecco's modified Eagle's medium (DMEM) was obtained from Nissui Pharmaceutical...

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“…CDs are amenable for regioselective or statistical modifications at the hydroxyl groups or the primary carbon atoms (C-6), respectively. The resulting CD derivatives, such as hydroxypropyl-CD, often show higher solubility in water and lower toxicity than the corresponding native CDs [20]. Amino functionalities have been multivalently attached to CDs via thioether linkages at the primary positions leading to highly water-soluble CD derivatives, which show improved binding affinities and aqueous solubilities compared to native CDs [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

Dandekar

Jain

Keil

et al. 2012

Journal of Controlled Release

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Cationic polyrotaxanes, obtained by temperature activated threading of cationic cyclodextrin derivatives onto water soluble cationic polymers (ionenes), form metastable nanometric polyplexes with pDNA and combinations of siRNA with pDNA.Because of their low toxicity, the polyrotaxane polyplexes constitute a very interesting system for the transfection of polynucleotides into mammalian cells. The complexation of Cy3-labeled siRNA within the polyplexes was demonstrated by fluorescence correlation spectroscopy. The uptake of the polyplexes (red) was imaged by confocal fluorescence microscopy using the A549 cell line as a model (blue: nuclei, green: membranes). The results prove the potential of polyrotaxanes for further investigations involving knocking down genes of therapeutic interest.

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Evaluation of the cytotoxicity of cyclodextrins and hydroxypropylated derivatives

Cited by 85 publications

References 14 publications

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

A Moderate Interaction of Maltosyl-α-cyclodextrin with Caco-2 Cells in Comparison with the Parent Cyclodextrin

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

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Evaluation of the cytotoxicity of cyclodextrins and hydroxypropylated derivatives

Cited by 85 publications

References 14 publications

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

A Moderate Interaction of Maltosyl-&alpha;-cyclodextrin with Caco-2 Cells in Comparison with the Parent Cyclodextrin

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

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A Moderate Interaction of Maltosyl-α-cyclodextrin with Caco-2 Cells in Comparison with the Parent Cyclodextrin