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Ionic agarose derivatives as polyelectrolytic additives for drug release.

Markus Witzler1, Margit Schulze2, Martin Gericke3

  • 1Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Straße 20, 53359 Rheinbach, Germany; Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University of Jena, Centre of Excellence for Polysaccharide Research, Humboldtstraße 10, 07743 Jena, Germany.

Carbohydrate Polymers
|November 30, 2025
PubMed
Summary

Ionic agarose derivatives were synthesized and applied in hydrogels for sustained drug delivery. These novel materials effectively reduced burst release and prolonged the release of various drugs over 14 days.

Keywords:
Agarose carbamatesAgarose derivatizationAgarose phenylcarbonatesAgarose sulfatesDrug releasePolyelectrolytesRelease kinetics

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Drug Delivery Systems

Background:

  • Polysaccharides are widely utilized as hydrogels in biomedical applications for drug release owing to their biocompatibility and inherent properties.
  • Agarose, a natural polysaccharide, offers thermoreversible gelling capabilities, making it a promising candidate for advanced drug delivery systems.
  • Developing functionalized polysaccharides with tunable properties is crucial for enhancing drug release profiles and therapeutic efficacy.

Purpose of the Study:

  • To synthesize and characterize novel anionic and cationic ionic agarose derivatives.
  • To investigate the application of these ionic agarose derivatives in composite scaffolds and layer-by-layer coatings for sustained drug release.
  • To evaluate the drug release kinetics using established and novel modeling approaches.

Main Methods:

  • Homogeneous derivatization of agarose in ionic liquid to produce anionic (agarose sulfates) and cationic (ammonium-bearing agarose carbamates) derivatives with controlled degrees of substitution.
  • Synthesis of agarose sulfates in a one-step process and cationic agarose carbamates via agarose phenylcarbonates.
  • Preparation of composite scaffolds with hydroxyapatite and layer-by-layer coated alginate microbeads using oppositely charged ionic agarose derivatives.
  • Incorporation and sustained release studies of adenosine triphosphate, suramin, methylene blue, and A740003 over 14 days.
  • Analysis of release curves using conventional models and two novel Langmuir-like models, assessing performance with Akaike's Information Criterion.

Main Results:

  • Successfully synthesized anionic and cationic ionic agarose derivatives with tunable degrees of substitution, retaining partial thermoreversible gelling behavior.
  • Ionic agarose derivatives incorporated into composite scaffolds and alginate microbeads significantly reduced burst release and sustained the release of multiple model drugs over 14 days.
  • Novel Langmuir-like models provided superior fitting and additional insights into the drug release mechanisms compared to commonly used models, as indicated by Akaike's Information Criterion.

Conclusions:

  • Ionic agarose derivatives represent a versatile platform for developing advanced hydrogel-based drug delivery systems.
  • The tunable nature and polyelectrolyte characteristics of these derivatives enable precise control over drug release kinetics, enhancing therapeutic outcomes.
  • The application of novel kinetic models is beneficial for a deeper understanding of drug release mechanisms from complex biomaterials.