Thiolated silicone oil: Synthesis, gelling and mucoadhesive properties

Partenhauser, Alexandra; Laffleur, Flavia; Rohrer, Julia; Bernkop‐Schnürch, Andreas

doi:10.1016/j.actbio.2015.01.020

Cited by 32 publications

(61 citation statements)

References 40 publications

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“…After the covalent attachment of free thiol groups on the polymeric backbone, the thiolated polymer can interact with the mucus layer and attach due to the formation of disulfide bonds (Leitner et al, 2003). An enhanced mucoadhesiveness has already been shown for thiolated silicone oil: MPA as well as cysteine was coupled as thiol ligands to a silicone oil side chain resulting in a prolonged residence time on small intestinal mucosa for up to 8 h (Partenhauser et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…This approach was modified for silicone oils as has recently been published by our research group (Partenhauser et al, 2015). In brief, 1 mmol (1 equiv.)…”

Section: Synthesis and Purification Of Thiolated Silicone Oilmentioning

confidence: 99%

“…For this study, dimethicone as well as an amino-modified polydimethylsiloxane polymer with a functional group equivalent weight of 4400, both with a viscosity of 100 cSt, and simethicone as standard antiflatulent were chosen as non-thiolated controls. For thiomer synthesis, the silicone oil with free primary amino groups on the side chain was coupled to the carboxylic acid group of MPA as a thiol ligand via carbodiimide reaction as described previously (Partenhauser et al, 2015). Due to the high viscosity of the thiomer, a self-emulsifying system for a homogenous silicone-MPA delivery was designed.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of thiolated silicone oil as advanced mucoadhesive antifoaming agent

et al. 2015

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Context: Silicone oils, such as dimethicone, are commonly administered against gastrointestinal gas accumulation and are attributed with mucoprotective features. Objective: Evaluation of thiolated silicone oil as advanced antiflatulence with a prolonged retention on small intestinal mucosa as an intended site of action. Materials and methods: 3-Mercaptopropionic acid (MPA) as a thiol ligand was covalently attached to silicone oil. This thiomer was assessed with regard to foam inhibiting action, droplet size of a suitable self-emulsifying system, mucoadhesion and cytotoxicity. Results: Antifoaming activity of silicone-MPA was complying with United States Pharmacopeia (USP) requirements for simethicone as standard antiflatulence. Another antifoaming test performed on porcine mucosa supported silicone-MPA's outstanding foam destruction, as this thiomer was superior in comparison to non-thiolated silicone oil and dimethicone with 14.7 ± 2.1 versus 73.3 ± 9.1 and 66.3 ± 7.5 s, respectively. A significantly enhanced mucoadhesiveness (p50.02) with 26.2 ± 7.1% silicone formulation remaining on small intestinal mucosa after 8 h was evident for the thiomer without any toxic effect. Conclusion: Thiolated silicone oil was found to exhibit excellent antifoaming and superior mucoadhesive features. The prolonged residence time of thiolated silicone oil promises to be beneficial in the treatment of flatulence, aerophagy and inflammation throughout the whole gastrointestinal tract.

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Section: Introductionmentioning

confidence: 99%

“…This approach was modified for silicone oils as has recently been published by our research group (Partenhauser et al, 2015). In brief, 1 mmol (1 equiv.)…”

Section: Synthesis and Purification Of Thiolated Silicone Oilmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of thiolated silicone oil as advanced mucoadhesive antifoaming agent

et al. 2015

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“…In rheological terms, a gel is defined when G 0 and G'' are frequency independent and tan is greater than 1. If G 0 is equal to G 0 at the crossover point, it means the polymer has as much elastic as viscous components (Partenhauser et al, 2015).…”

Section: Rheological Assaymentioning

confidence: 99%

In vitroevaluation of thio-poly acrylic acid for intraoral delivery

2015

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Context: Intraoral drug delivery as mucosal delivery pathway provides a huge platform in the pharmaceutical field. Objective: Combining mucoadhesiveness and controlled release of thio-poly acrylic acid as advanced excipient for buccal drug delivery. Materials and methods: Mediated by carbodiimide, cysteine was covalently attached to poly acrylic acid. This thiomer was assessed with regard to cytotoxicity, stability, mucoadhesion, and rheology as well as release behavior of Lidocaine. Results: Stability assays of thio-poly acrylic acid were complying with United States Pharmacopeia requirements. Mucoadhesion assay such as tensile (total work of adhesion), bioadhesion, rotating cylinder revealed as this thiomer was superior in comparison to nonthiolated poly acrylic acid with 7.61-fold, 2.8-fold, 5.61-fold improvement, respectively without any toxic effect. The cell viability exhibited over 90% after incubation time of 3 h and 24 h respectively. Lidocaine release showed 1.98-fold more controlled release over 3 h in comparison to unmodified poly acrylic acid. Conclusion: Taken the findings in consideration, thio-poly acrylic acid provides excellent stability, controlled release, and superior mucoadhesive features. The prolonged residence time of thio-poly acrylic acid represents a pillar in the buccal drug delivery.

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“…The potential cytotoxic effect of 0.25% and 0.375% (w/v) SEDDS formulations was determined by a slightly modified resazurin assay as described previously (Partenhauser et al, 2015). Approximately 2.5 Â 10 4 Caco-2 cells per well were seeded to a 24-well plate.…”

Section: Resazurin Assaymentioning

confidence: 99%

Development andin vitroevaluation of an oral SEDDS for desmopressin

et al. 2016

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Context: Self-emulsifying drug delivery systems (SEDDS) are among most promising tools for improving oral peptide bioavailability. Objective: In this study, in vitro protective effect of SEDDS containing desmopressin against presystemic inactivation by glutathione and a-chymotrypsin was evaluated. Materials and methods: The partitioning coefficient (log P) of desmopressin was increased via hydrophobic ion pairing using anionic surfactants. Solubility studies were performed to select the appropriate solvents for SEDDS preparation. Subsequently, droplet size and emulsification properties of 22 SEDDS formulations were evaluated. Moreover, the peptide-surfactant complex was dissolved in two chosen SEDDS formulations. Finally, SEDDS containing desmopressin were characterized regarding lipase stability, toxicity, and in vitro protective effect toward glutathione and a-chymotrypsin. Results: Desmopressin log P was increased from initial À6.13 to 0.33 using sodium docusate. The resulting desmopressin docusate complex (DES/AOT) was incorporated in two different SEDDS formulations, containing Capmul 907 P as main solvent. DES/AOT-SEDDS-F4 (containing 0.07% w/w DES/AOT) was composed of 50% Capmul 907P, 40% Cremophor RH40, and 10% Transcutol. The comparatively more hydrophilic formulation DES/AOT-SEDDS-F15 (containing 0.25% w/w DES/AOT) consisted of 20% Capmul 907P, 40% Acconon MC8-2, and 40% Tween 20. Both formulations were stable toward digestion by lipase and protected desmopressin toward a-chymotrypsin degradation. Moreover, DES/AOT-SEDDS-F4 also protected the peptide from thiol/disulfide exchange reactions with glutathione and was not cytotoxic at a concentration of 0.375% (w/w). Conclusion: DES/AOT-SEDDS-F4 protected desmopressin from in vitro glutathione and a-chymotrypsin degradation. DES/AOT-SEDDS-F4 was metabolically stable and nontoxic. Therefore, it could be considered as a potential delivery system for oral desmopressin administration.

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Thiolated silicone oil: Synthesis, gelling and mucoadhesive properties

Abstract: Graphical abstract

Cited by 32 publications

References 40 publications

Evaluation of thiolated silicone oil as advanced mucoadhesive antifoaming agent

Evaluation of thiolated silicone oil as advanced mucoadhesive antifoaming agent

In vitroevaluation of thio-poly acrylic acid for intraoral delivery

Development andin vitroevaluation of an oral SEDDS for desmopressin

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