Posted by This study comprehensively evaluates three generations of thiolated cyclodextrins (CDs). Free thiol groups of thiolated γ-CDs (CD-SH) were S-protected with 2-mercaptonicotinic acid (MNA), leading to a second generation of thiolated CDs (CD-SS-MNA) and with 2 kDa polyethylene glycol (PEG) bearing a terminal thiol group leading to a third generation of thiolated CDs (CD-SS-PEG). The findings demonstrate a 9 to 12-fold enhancement in mucoadhesion for thiolated CDs compared to native CD, highlighting the potential of these modified CDs in drug delivery applications. The research confirms that S-protected thiolated CDs exhibit superior mucoadhesive properties compared to their non-protected counterparts. The protection of free sulfhydryl moieties not only influences the mucoadhesive strength of thiolated CDs but also affects their diffusion through the mucosal layer due to the reduced reactivity of thiol groups. The results show a rank order for mucosal diffusion as follows: CD-SH < CD-SS-MNA < CD-SS-PEG. These findings emphasize the importance of S-protection in thiolated CDs to prevent premature disulfide bond formation on the mucosa or at the luminal site of the loose outer mucosal surface. By ensuring that thiol groups remain available for longer periods, S-protection enables intimate contact between thiolated CDs and mucosal membranes, particularly close to the endothelial site. This intimate contact is crucial for enhancing the attachment of drug delivery systems onto mucosal surfaces and improving the overall performance of mucoadhesive carriers. In summary, this study provides valuable insights into the role of S-protection in thiolated cyclodextrins and its potential to improve the mucoadhesive properties of drug delivery systems.
Soheil Haddadzadegan, Patrick Knoll, Richard Wibel, Gergely Kali, Andreas Bernkop-Schnürch (2023)
Three generations of thiolated cyclodextrins: A direct comparison of their mucus permeating and mucoadhesive properties. Acta Biomaterialia 167, 309-320.
https://doi.org/10.1016/j.actbio.2023.05.050
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