Thiolated α-cyclodextrin: The likely smallest drug carrier providing enhanced cellular uptake and endosomal escape

Kaplan, Özlem; Truszkowska, Martyna; Kali, Gergely; Knoll, Patrick; Blanco Massani, Mariana; Braun, Doris Elfriede; Bernkop-Schnürch, Andreas

doi:10.1016/j.carbpol.2023.121070

Cited by 5 publications

(9 citation statements)

References 45 publications

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“…In contrast, β-CD-SH displayed improved cellular uptake compared with the native form. The presence of thiol groups facilitates interactions with the cell membrane, leading to increased internalization, as was expected based on previous studies . Furthermore, β-CD-SS-MESNA showed further improvement in cellular uptake compared to β-CD-SH.…”

Section: Resultssupporting

confidence: 78%

“…Previous studies showed a slightly higher, 5-fold cellular uptake enhancement by the thiolation of the native α-CD (RMFI 50). For our products, based on the native β-CD with RMFI 60, the 3-fold increase led to an RMFI value of 180, which is in a similar order of magnitude as the cellular uptake using α-CD-SH . Even though the mechanism of thiol-mediated cellular uptake of CDs is not explored in detail, it is already known that the free thiol groups, as well as disulfides, enhance the cellular uptake through disulfide bond formation with exofacial thiols of the cell membrane proteins.…”

Section: Resultsmentioning

confidence: 64%

“…As shown in Figure A, low cellular uptake was found for all CDs at 4 °C without significant difference. In contrast, at 37 °C, the cellular uptake increased for all of the CDs (Figure B), likely due to the energy-driven endocytosis pathway . Significant differences in the cellular uptake of applied CDs were found at this temperature.…”

Section: Resultsmentioning

confidence: 86%

“…The interaction of the β-CD and its derivatives with the cellular membrane also increased the cellular uptake . Our previous paper demonstrated that thiolation of α-CD enhances the cellular uptake . In order to better understand the cytotoxicity of the synthesized CDs, the cellular uptake of β-CD, β-CD-SH, and β-CD-SS-MESNA/coumarin-6 complexes was analyzed and quantified by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

“…Flow Cytometry. Flow cytometry was measured as previously reported by Kaplan et al 33 Caco-2 cells were seeded in a 24-well plate and incubated for 14 days at 37 °C under 5% CO 2 and a 95% relative humidity environment. Complexes of coumarin-6 and native β-CD, β-CD-SH, or β-CD-SS-MESNA (0.05% m/v) dissolved in HEPES buffer were applied to the cells and incubated for 3 h at 4 or 37 °C.…”

Section: ■ Introductionmentioning

confidence: 99%

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Enhanced Mucoadhesion of Thiolated β-Cyclodextrin by S-Protection with 2-Mercaptoethanesulfonic Acid

Kali,

Taha,

Campanella

et al. 2024

ACS Omega

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This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with phosphorus pentasulfide resulting in a thiolated β-CD (β-CD-SH) and subsequently Sprotected with 2-mercaptoethanesulfonate (MESNA) to form β-CD-SS-MESNA. The structure of the novel excipient was confirmed by 1 H NMR and Fourier-transform infrared spectroscopy. The sulfhydryl content of β-CD-SH, determined by Ellman's test, was 2281.00 ± 147 μmol/g, and it was decreased to 45.93 ± 19.40 μmol/g by Sprotection. Due to thiolation and S-protection, the viscosity of the mixture of mucus with β-CD-SH and β-CD-SS-MESNA increased 1.8 and 4.1-fold, compared to native β-CD, respectively. The unprotected β-CD-SH diffused to a lesser extent into the mucus than native β-CD, while S-protected β-CD-SS-MESNA showed the highest mucodiffusion among the applied CDs. A 1.5-and 3.0-fold higher cellular uptake of β-CD-SH and β-CD-SS-MESNA, compared to the native one, was established on Caco-2 cell line by flow cytometry, respectively, causing slightly decreased cell viability. On account of the enhanced mucoadhesion, this higher cellular uptake does not affect the application potential of β-CD-SS-MESNA as an oral drug delivery system since the carrier remains in the mucus and does not reach the underlying epithelial layer. According to these results, the S-protection of β-CD-SH with MESNA promotes improved mucodiffusion, strong mucoadhesion, and prolonged mucosal residence time.

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Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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