Anhydrous thiomers: Strategy for enhanced mucoadhesion

Area of Science:

• Polymer Chemistry
• Materials Science
• Biomaterials Engineering

Background:

• Traditional thiolation of hydrophilic polymers occurs in aqueous media, leading to polymer chain entanglement and affecting mucoadhesive properties.
• The influence of polymer network structure (entanglement, porosity) and functionalization degree on mucoadhesion is not fully understood when synthesized in water.

Purpose of the Study:

• To investigate the impact of anhydrous synthesis conditions on the mucoadhesive properties of thiolated poly(acrylic acid) (PAA).
• To compare the mucoadhesive characteristics of PAA synthesized in the absence of water versus in aqueous media.

Main Methods:

• Developed anhydrous synthesis and purification methods for immobilizing l-cysteine (PAA-Cys) and 2-mercaptonicotinic acid (PAA-Cys-MNA) onto PAA.
• Characterized the synthesized conjugates chemically and determined their particle size.
• Assessed mucoadhesive properties using residence time and tensile strength measurements on porcine intestinal mucosa.

Main Results:

• Anhydrous products showed significantly higher levels of immobilized thiol groups (4.2-fold for PAA-Cys) and MNA (3.1-fold for PAA-Cys-MNA).
• Particle size had a negligible effect on mucoadhesion.
• Anhydrous synthesis led to substantial increases in residence time (2.5-fold for PAA-Cys, 21.2-fold for PAA-Cys-MNA) and work of adhesion (2.9-fold for PAA-Cys, 5.1-fold for PAA-Cys-MNA).

Conclusions:

• Anhydrous synthesis conditions are a promising strategy for enhancing the modification rates of hydrophilic polymers.
• This approach leads to significantly improved mucoadhesive properties compared to conventional aqueous synthesis methods.