Synthesis and characterization of thiolated β-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery

Ijaz, Munazza; Matuszczak, Barbara; Rahmat, Deni; Mahmood, Arshad; Bonengel, Sonja; Hussain, Shah; Huck, Christian W.; Bernkop‐Schnürch, Andreas

doi:10.1016/j.carbpol.2015.06.073

Cited by 57 publications

(32 citation statements)

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“…to gastrointestinal tract (GIT), accordingly, cannot assure localization of dosage forms [12,13].A feasible new era of mucoadhesive polymers are thiolated polymers [14], (bearing thiol side chain) alleged thiomers have proven to be a promising new class of polymeric excipients. Instead of entrenched polymers, thiomers can form strong covalent bonds via thiol/disulfide exchange reactions with cysteine-rich subdomains of mucus [15][16][17]. As per the need, thiomers ensure the localization of the dosage form for an extended time with good biodegradation.…”

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confidence: 99%

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Naveen¹,

Gopinath

Kurakula

2020

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The success of mucoadhesive drug delivery systems relies on the type of polymer used, which becomes adhesive naturally upon hydration. Intended polymers should be able to maintain prolonged contact with biological membranes, and to protect or cater the drug to a prolonged period. Most of the hydro polymers form weak non-covalent bonds, that hinder localization of dosage forms at specific sites resulting in therapeutic inefficiency. This can be overcome by the thiol functionalization of natural polymers. In the present study, natural okra gum (OG) was extracted, followed by thiolation (TOG) and evaluated for mucoadhesion property and its role in enhancing the efficacy of repaglinide as a model drug (short-acting Type II antidiabetic drug). The thiol functionalization of OG (TOG) was confirmed by a Fourier-transform infrared spectroscopy (FTIR) study that showed a polyhedral to a spherical shape that had a rougher surface. Differential scanning calorimetry (DSC) and X-Ray Diffraction (XRD) studies of TOG indicated a decline in endothermic transition temperature and high crystallinity, respectively, in comparison to OG. CSFR (Crushing Strength: Friability Ratio), weight and thickness variations of repaglinidetablets formulated using TOG were >80% and <2.5% respectively. The highest swelling index (107.89 ± 1.99%) and strong mucoadhesion due to high disulfide bonds were observed for repaglinide TOG tablets in comparison to RG OG tablets. In-vitro release studies indicated a controlled drug release from thiolated formulations proportional to the concentration of thiomers that have a good correlation with in-vivo studies. Pharmacokinetic studies indicated higher AUC (area under the curve), longer t 1/2 with thiomers. and Level A IVIV (in vitro in vivo) correlation was established from the bioavailability and dissolution data. Consequently, all the obtained results suggest that thiomers based formulations can be promising drug delivery systems, even in targeting onerous mucosal surfaces like nasal, ocular or vaginal.by suitable approaches such as thiolation, to employ in mucoadhesion drug delivery systems [9]. Nevertheless, to date, there has been no research reported in demonstrating the synthesis of thiolated okra gum (TOG) and evaluating its use in designing mucoadhesive drug delivery systems.The term bio adhesion depicts the adhesion of the polymer to the biological membrane. Specifically, when the adhesion is limited to the mucosal surface it is named mucoadhesion [10]. The conception of mucoadhesion, as well as mucoadhesion polymers, was developed in the mid 1980s as an intriguing methodology especially for targeting the delivery of drugs at a site or at the absorption window. Mucoadhesive polymers become adhesive on hydration and characterized to have prolonged contact and residence time with the mucous membrane. [11]. Despite a few notable exceptions, gastric mucoadhesive systems do not reach their full potential. The success of the majority of the first generation mucoadhesion polymers was limited owing to thei...

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confidence: 99%

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Naveen¹,

Gopinath

Kurakula

2020

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“…The intestinal residence time was assessed for G, Gox, GSH 1 and 2 following a procedure previously described and slightly modified (Ijaz et al, 2015). Porcine small intestine was obtained from a local abattoir and cut into slice of 2 cm length and 1 cm width.…”

Section: Intestinal Residence Time Testmentioning

confidence: 99%

Thiolated graphene oxide as promising mucoadhesive carrier for hydrophobic drugs

Sousa

Buttenhauser

Suchaoin

et al. 2016

International Journal of Pharmaceutics

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“…For comparison, a cationic thiolated β-CD was synthesized in a two-step synthetic pathway by oxidizing diol groups of CD with NaIO 4 , followed by covalent coupling of cysteamine via reductive amination. 1 International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 44.224.250.200 on For personal use only.…”

Section: Synthesis Of a Cationic Thiolated β-Cdmentioning

confidence: 99%

“…Cyclodextrins (CDs) are considered as probably the smallest polymeric backbone for thiomers representing some of the most broadly considered mucoadhesive excipients. 1,2 Because of the ability of thiol groups to form disulfide bonds with mucus glycoproteins covering mucosal membranes, 3 thiomers are covalently attached to the mucus layer. 4,5 These unique properties guarantee the benefits of prolonged drug residence time on specific target mucosal tissues and a consequently more efficient local therapy.…”

Section: Introductionmentioning

confidence: 99%

“…These cationic thiolated CDs, however, showed a significant toxic effect on cells. 1,2 In addition, an unintended pH-dependent drug release and even incompatibility with anionic drugs are expected consequences. 9 Having on one hand the strongly prolonged mucosal residence time of thiolated CDs and taking on the other hand the drawbacks of synthesis via oxidative-ring opening and reductive amination into account, it was therefore the aim of this study to generate thiolated CDs via an alternative synthetic pathway.…”

Section: Introductionmentioning

confidence: 99%

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Non-ionic thiolated cyclodextrins — the next generation

Moghadam¹,

Ijaz²,

Asim³

et al. 2018

IJN

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IntroductionThe current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery.Materials and methodsThiolated beta CD (β-CD) was prepared through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. The thiolated β-CD was characterized in vitro via dissolution studies, cytotoxicity studies, mucoadhesion studies on freshly excised porcine intestinal mucosa, and inclusion complex formation with miconazole nitrate.ResultsThiolated β-CDs namely β-CD-SH600 and β-CD-SH1200 displayed 558.66 ± 78 and 1,163.45 ± 96 µmol thiol groups per gram of polymer, respectively. Stability constant (Kc) of 190 M-1 confirmed the inclusion complex formation of miconazole nitrate with β-CD-SH. Inclusion complexes of β-CD-SH600 and β-CD-SH1200 resulted in 157- and 257-fold increased solubility of miconazole nitrate, respectively. In addition, more than 80% of thiol groups were stable even after 6 hours at pH 5. Both β-CD-SH compounds showed at least 1.3-fold improved solubility in water. In contrast to cationic thiolated CDs of the first generation, both thiomers showed no significant cytotoxicity. The mucoadhesive properties of the new thiolated CDs were 39.73- and 46.37-fold improved, respectively.ConclusionThese results indicate that β-CD-SH might provide a new favorable tool for delivery of poorly soluble drugs providing a prolonged residence time on mucosal surfaces.

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Synthesis and characterization of thiolated β-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery

Cited by 57 publications

References 28 publications

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Thiolated graphene oxide as promising mucoadhesive carrier for hydrophobic drugs

Non-ionic thiolated cyclodextrins — the next generation

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Synthesis and characterization of thiolated β-cyclodextrin as a novel mucoadhesive excipient for intra-oral drug delivery

Cited by 57 publications

References 28 publications

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Thiolated graphene oxide as promising mucoadhesive carrier for hydrophobic drugs

Non-ionic thiolated cyclodextrins &mdash; the next generation

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Non-ionic thiolated cyclodextrins — the next generation