Mucoadhesive polymers: Design of S-protected thiolated cyclodextrin-based hydrogels

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Cyclodextrins (CDs) are widely used in drug delivery.
• Thiolated CDs offer enhanced properties compared to native CDs.
• Hydrogels provide a versatile platform for drug encapsulation and release.

Purpose of the Study:

• To design and synthesize chemically crosslinked thiolated cyclodextrin-based hydrogels.
• To evaluate the mucoadhesive properties of these hydrogels.
• To assess their potential for controlled drug release.

Main Methods:

• Synthesis of S-protected thiolated β-cyclodextrin (β-CD-SH) using MESNA.
• Crosslinking of β-CD-SH with citric acid to form hydrogels.
• Characterization of hydrogels via rheology, mucoadhesion studies (mucosal residence time), and cytotoxicity assays (hemolysis, resazurin assay).
• In vitro release studies using ritonavir as a model drug.

Main Results:

• The synthesized S-protected β-CD-SH hydrogels exhibited significantly reduced hemolysis and minor cytotoxicity.
• Rheological studies showed a substantial increase in viscosity for thiolated CD hydrogels compared to native CD hydrogels.
• Mucosal residence time studies demonstrated a 16.6-fold and 2.4-fold lower removal from porcine intestinal and buccal mucosa, respectively, for thiolated CD hydrogels.
• Sustained release of ritonavir was observed from the thiolated β-CD-based hydrogels.

Conclusions:

• S-protected thiolated β-CD-based hydrogels possess superior mucoadhesive properties.
• These hydrogels exhibit excellent drug release-controlling capabilities.
• The developed hydrogels represent promising systems for effective mucosal drug delivery.