Thiolated cyclodextrins: A comparative study of their mucoadhesive properties

Area of Science:

• Materials Science
• Polymer Chemistry
• Pharmaceutical Sciences

Background:

• Cyclodextrins (CDs) are versatile cyclic oligosaccharides with applications in drug delivery.
• Modifying CDs via thiolation can alter their physicochemical and mucoadhesive properties.
• Understanding the impact of thiolation degree and charge on CD mucoadhesion is crucial for optimizing delivery systems.

Purpose of the Study:

• To compare the mucoadhesive properties of nonionic, negatively, and positively charged thiolated cyclodextrins (CDs).
• To investigate the influence of low and high degrees of thiolation on α-, β-, and γ-CDs.
• To evaluate the cytotoxicity and mucoadhesive performance of various thiolated CD formulations.

Main Methods:

• Synthesis of thiolated CDs (CD-SH, CD-Cya, CD-MSA) with varying degrees of thiolation.
• Characterization using 1H NMR and Ellman's test.
• Cytotoxicity assessment via resazurin and hemolysis assays.
• Mucoadhesion evaluation through rheological studies with porcine mucus and residence time studies on porcine intestinal mucosa.

Main Results:

• Thiolation was confirmed, with degrees ranging from 243 to 3379 µmol/g depending on the method and CD type.
• Only cationic CDs exhibited cytotoxicity.
• Nonionic, highly thiolated CDs showed significantly improved dynamic viscosity with mucus (5.6- to 17.8-fold increase).
• All thiolated CDs prolonged mucosal residence time, with γ-CDs showing the greatest effect.

Conclusions:

• A high degree of thiolation is a key factor for enhanced mucoadhesive properties.
• The introduction of cationic charges also significantly contributes to improved mucoadhesion.
• Thiolated cyclodextrins, particularly highly thiolated and cationic variants, show promise for mucoadhesive drug delivery systems.