Thiolated cyclodextrins: A comparative study of their mucoadhesive properties

Fürst, Andrea; Kali, Gergely; Efiana, Nuri Ari; Akkuş‐Dağdeviren, Zeynep Burcu; Haddadzadegan, Soheil; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ijpharm.2023.122719

Cited by 10 publications

(16 citation statements)

References 28 publications

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“…The suspensions/solutions and porcine mucus were mixed and homogenized in a ratio of 1:5. After incubation of 4 h at 37 °C without stirring, samples were analyzed, determining the viscoelastic characteristics …”

Section: Methodsmentioning

confidence: 99%

“…The use of cationic substructures in drug delivery is mostly undesired because of the potential cytotoxicity of the positively charged groups. Recently, a novel thiolation method was described by our group in order to form anionic thiomers of lower toxicity . By covalent attachment of 2-mercaptosuccinic acid (MSA) to oligosaccharides, highly mucoadhesive thiomers were obtained.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, a novel thiolation method was described by our group in order to form anionic thiomers of lower toxicity. 17 By covalent attachment of 2-mercaptosuccinic acid (MSA) to oligosaccharides, highly mucoadhesive thiomers were obtained.…”

Section: ■ Introductionmentioning

confidence: 99%

“…After incubation of 4 h at 37 °C without stirring, samples were analyzed, determining the viscoelastic characteristics. 17 Permeation-Enhancing Properties. In Vitro Permeation Studies on the Caco-2 Cell Monolayer.…”

Section: ■ Introductionmentioning

confidence: 99%

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Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Kali,

Özkahraman,

Laffleur

et al. 2023

Biomacromolecules

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This study aims to design an anionic, thiolated cellulose derivative and to evaluate its mucoadhesive and permeation-enhancing properties utilizing enoxaparin as a model drug. 2-Mercaptosuccinic acid-modified cellulose (cellulose− mercaptosuccinate) was synthesized by the reaction of cellulose with S-acetylmercaptosuccinic anhydride. The chemical structure of the target compound was confirmed by FTIR and 1 H NMR spectroscopy. The thiol content was determined by Ellman's test. The conjugate exhibited 215.5 ± 25 μmol/g of thiol groups and 84 ± 16 μmol/g of disulfide bonds. Because of thiolation, mucoadhesion on porcine intestinal mucosa was 9.6-fold enhanced. The apparent permeability (P app ) of the model dye Lucifer yellow was up to 2.2-fold improved by 0.5% cellulose−mercaptosuccinate on a Caco-2 cell monolayer. Enoxaparin permeation through rat intestinal mucosa increased 2.4-fold in the presence of 0.5% cellulose−mercaptosuccinate compared with the drug in buffer only. In vivo studies in rats showed an oral bioavailability of 8.98% using cellulose−mercaptosuccinate, which was 12.5fold higher than that of the aqueous solution of the drug. Results of this study show that the modification of cellulose with 2mercaptosuccinic acid provides mucoadhesive and permeation-enhancing properties, making this thiolated polymer an attractive excipient for oral drug delivery.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Kali,

Özkahraman,

Laffleur

et al. 2023

Biomacromolecules

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“…Thiolated CDs are investigated mostly for ocular and oral drug delivery. ,, They can be generated by covalent attachment of thiol-containing ligands − or direct hydroxyl-to-thiol conversions. − ,,, The latter is preferred because it does not alter the CDs’ characteristics, such as its complexation ability or cytotoxicity . A crucial factor for mucoadhesion is the degree of thiolation, as the more the hydroxyls exchanged with thiol groups, the stronger mucoadhesion. ,, Recently, our research group described a thiolation process, applying phosphorus pentasulfide, and reached an up to 100% degree of thiolation . This per-thiolated β-cyclodextrin (β-CD) presented up to 89-fold enhancement in mucoadhesive properties in vitro and also highly prolonged gastrointestinal residence time in vivo. , Despite these advantageous mucoadhesive properties, the aqueous solubility of thiolated β-CDs is similar or lower than that of the native CD.…”

Section: Introductionmentioning

confidence: 99%

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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Three generations of thiolated cyclodextrins: A direct comparison of their mucus permeating and mucoadhesive properties

Haddadzadegan,

Knoll,

Wibel

et al. 2023

Acta Biomaterialia

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Thiolated cyclodextrins: A comparative study of their mucoadhesive properties

Cited by 10 publications

References 28 publications

Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

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

Three generations of thiolated cyclodextrins: A direct comparison of their mucus permeating and mucoadhesive properties

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