Elucidating the Structure-Function Relationship of Solvent and Cross-Linker on Affinity-Based Release from...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Antimicrobial Research

Background:

• Minocycline (MNC) is a broad-spectrum antibiotic effective for implant infections.
• Conventional hydrogel formulations exhibit biphasic drug release, limiting sustained antimicrobial action.
• Polymerized cyclodextrin (pCD) hydrogels offer potential for controlled localized drug delivery.

Purpose of the Study:

• To develop and characterize pCD hydrogels for sustained release of MNC.
• To evaluate the loading capacity, release kinetics, and antimicrobial efficacy of MNC-loaded pCD hydrogels.
• To investigate the influence of crosslinking density and solvent polarity on MNC loading and release.

Main Methods:

• Insoluble pCD hydrogels were synthesized with varying crosslinking densities.
• MNC loading and release profiles were quantified over time.
• Antimicrobial activity against Staphylococcus aureus and Escherichia coli was assessed.
• Drug-CD association was studied using water/ethanol solvent mixtures.

Main Results:

• pCD hydrogels achieved MNC loading of 5-12 wt % with release exceeding 14 days.
• Sustained antimicrobial activity was observed for >40 days against S. aureus and >70 days against E. coli.
• Increased crosslinking and decreased solvent polarity reduced MNC loading, with solvent polarity showing a significant independent effect.

Conclusions:

• pCD hydrogels provide a promising platform for sustained localized delivery of minocycline.
• The developed system significantly extends antimicrobial efficacy against key pathogens.
• Solvent polarity is a critical factor influencing drug loading in pCD hydrogels, independent of swelling.