Evaluation of Buccal Methyl-β-Cyclodextrin Toxicity on Human Oral Epithelial Cell Culture Model

Boulmedarat, Laila; Bochot, Amélie; Lesieur, Sylviane; Fattal, Elias

doi:10.1002/jps.20350

Cited by 51 publications

(28 citation statements)

References 36 publications

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“…Hydrophilic cyclodextrins, which are considered a new class of penetration enhancers, improve drug delivery through the membranes by increasing the availability of dissolved drug close to the membrane surface (7,8). Methylated β-cyclodextrin interacts strongly with lipids and modify mucosa permeability (9). Some toxicological effects can be expected if higher concentrations of CDs are used due to its high affinity to lipids (10).…”

Section: Introductionmentioning

confidence: 99%

“…Some toxicological effects can be expected if higher concentrations of CDs are used due to its high affinity to lipids (10). However, cyclodextrin is very effective as penetration enhancers at low concentrations ranging from 2% to 5% (7) therefore avoiding harmful effects (9). The modified methyl-β-cyclodextrin (MβCD) offers a significant advantage, as a host molecule, over the beta-cyclodextrin β-CD since its solubility in aqueous solution at room temperature (>2,000 mg/mL) is significantly higher than the latter one (18.5 mg/mL) (6).…”

Section: Introductionmentioning

confidence: 99%

“…MCZ inclusion complexes with MβCD can be very interesting due to superior solubility of this cyclodextrin, enhancing permeation effect through biological membranes (18) and an overall improvement of the efficacy of drug delivery systems. MβCD has been shown to be an effective promoter of drug absorption by increasing drug penetration through the skin and nasal (8) and buccal mucosa (9).…”

Section: Introductionmentioning

confidence: 99%

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Preparation and Solid-State Characterization of Inclusion Complexes Formed Between Miconazole and Methyl-β-Cyclodextrin

et al. 2008

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Abstract. The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin (MβCD) and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) in aqueous solution by phase solubility studies. Inclusion complexes with MβCD in the solid state were then prepared by different methods, i.e., kneading, coevaporation (COE), spray-drying (SD), and lyophilization (LPh). The physicochemical properties of these complexes were subsequently studied by means of differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction techniques. Phase solubility diagrams with MβCD and HPβCD were classified as A P type, indicating the formation of 1:1 and 1:2 stoichiometric inclusion complexes. The apparent stability constants (K S ) calculated from the phase solubility diagram were 145.69 M −1 (K 1:1 ) and 11.11 M −1 (K 1:2 ) for MβCD and 126.94 M −1 (K 1:1 ) and 2.20 M −1 (K 1:2 ) for HPβCD. The method of preparation of the inclusion complexes in the solid state was shown to greatly affect the properties of the formed complex. Hence, the LPh, SD, and COE methods produce true inclusion complexes between MCZ and MβCD. In contrast, crystalline drug was still clearly detectable in the kneaded (KN) product.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preparation and Solid-State Characterization of Inclusion Complexes Formed Between Miconazole and Methyl-β-Cyclodextrin

et al. 2008

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“…RHE tissues have been used extensively previously for biocompatibility studies and as a model system for investigating microbial pathogenicity. [65][66][67][68][69][70] RHE tissues are structurally more complex than keratinocyte monolayers and more closely resemble the physiological environment of the oral cavity. A range of concentrations of Ecasol were applied to the surface of RHE tissue samples for 1 h periods, and following removal of Ecasol and washing with PBS, viability was assessed using the Alamar Blue assay.…”

Section: Discussionmentioning

confidence: 99%

Lack of cytotoxicity by Trustwater Ecasol™ used to maintain good quality dental unit waterline output water in keratinocyte monolayer and reconstituted human oral epithelial tissue models

Boyle

O’Donnell

Russell

et al. 2010

Journal of Dentistry

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“…Early studies reported only minimal toxicity for CDs used to deliver lipophilic substances to cells in culture Epa et al, 2000) as well as in the intrathecal/intracerebral delivery of hydrophobic drugs (Yaksh et al, 1991;Jang et al, 1992;Yamamoto and Yaksh, 1992). For instance, the cytotoxic effects of MβCD have been assessed in cultures of human skin fibroblasts for periods of up to 144 h without reported increase in lactate dehydrogenase activity measured in the culture media (Pfitzner et al, 2000;Boulmedarat et al;. However, as the interest to use these molecules intensifies, there is an increased interest in further evaluating potential negative effects of CDs on cell viability considering the role of these molecules in depleting cholesterol from the cell membrane (Schonfelder et al, 2006;Bar-On et al, 2006;Li et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Characterization of methyl-β-cyclodextrin toxicity in NGF-differentiated PC12 cell death

et al. 2007

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Cyclodextrins (CDs) are used to deliver hydrophobic molecules in aqueous environments. Methyl-β-cyclodextrin (MβCD), a member of this family of molecules, has been proposed to be a good carrier to deliver fatty acids to cells in culture. This report focuses on studying the in vitro effects of MβCD on nerve growth factor-differentiated PC12 (NGFDPC12) cells, a tissue culture model to study neuronal survival and differentiation. The main findings are: (1) NGFDPC12 cells have normal viability when exposed to 0.12% MβCD but showed a significant loss in cell viability at higher concentrations; (2) NGFDPC12 cells exposed to 0.25% MβCD exhibit nuclear condensation, blebbing and apoptotic bodies, and whole cell lysates exhibited an increase in caspase-3-like activity and high levels of Bax and Bcl-X L protein expression compared to control. Cultures treated with 0.25% MβCD also showed cleavage of normal 21-kDa Bax protein into a 18-kDa fragment. (3) Experiments using 0.12% MβCD to deliver oleic acid did not affect cell viability, in contrast NGFDPC12 cultures in which 0.25% MβCD concentration is used exhibited similar loss of cell viability as observed with 0.25% MβCD alone. Treating these cultures with caspase-3 inhibitor z-VAD-fmk did not protect the cells from MβCD toxic effects. (4) Immortalized Schwann cells (iSC) exposed to MβCD 0.12% did not show loss of cell viability while 0.25% MβCD triggered a significant toxicity but with a different dose and time course dynamic than NGFDPC12 cells. Thus, NGDPC12 or iSC cell cultures exposed to 0.12% MβCD exhibits normal viability while higher concentrations increase in cell death and apoptosis.

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Evaluation of Buccal Methyl-β-Cyclodextrin Toxicity on Human Oral Epithelial Cell Culture Model

Cited by 51 publications

References 36 publications

Preparation and Solid-State Characterization of Inclusion Complexes Formed Between Miconazole and Methyl-β-Cyclodextrin

Preparation and Solid-State Characterization of Inclusion Complexes Formed Between Miconazole and Methyl-β-Cyclodextrin

Lack of cytotoxicity by Trustwater Ecasol™ used to maintain good quality dental unit waterline output water in keratinocyte monolayer and reconstituted human oral epithelial tissue models

Characterization of methyl-β-cyclodextrin toxicity in NGF-differentiated PC12 cell death

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