One method used to deliver drugs in a controlled manner is to encapsulate them in an injectable gel. Microgels — hydrogel particles made of synthetic or natural polymers with a high water content that measure about 1 to 100 micrometers wide — are garnering increased attention for drug delivery. The release of encapsulated drugs can be precisely controlled (called programmable delivery) by modifying the microgel properties, such as particle size, swelling behavior and the degree of cross-linking. Multiple drugs can be incorporated into one injection, which can help limit invasiveness, particularly with complex medical treatments.
Manufacture of microgels is typically a complex process involving carefully developing covalent bonds. Now, a research team at the University of Michigan (UM; Ann Arbor, Mich.; www.che.engin.umich.edu) has developed an alternative, simpler method for making microgels using ionic bonds, which are easier to break than covalent bonds.
“A microgel suspension behaves in part like a solid with the controlled delivery, and in part like a liquid with its flexibility, making it an ideal form for injections,” said Albert Liu, an assistant professor of chemical engineering, macromolecular science and engineering and materials science and engineering at UM and corresponding author of the study.
The process developed by the team combines alginate — a naturally occurring carbohydrate in brown algae like kelp — with calcium to form a microgel. The gel is then treated in baths with different ions like magnesium or sodium, which replace the tight calcium-alginate bond with a bond that is easier to break.
The ratio of calcium to magnesium or sodium ions within the microgels can be precisely controlled by adjusting the bath treatments, including concentrations of the ion baths and duration of the treatment. The ratio dictates the mesh size of the polymer gel — the space between cross-linked polymer chains — which in turn controls the drug release rate. Multiple pre-programmed release profiles can be obtained by mixing and matching different post-synthesized ionic exchanged microgels into larger gel capsules. Physical properties that affect drug release times, such as surface roughness, swelling behavior and the ion distribution, were characterized by microscopy.
The research team demonstrates drug release profiles with brightly colored test drugs for easy tracking. The study showcases how varying ion-exchange treatments achieve programmable release patterns.
“The parameter space is immense and I’m sure we can continue to optimize the method further,” said Jihpeng Sun, a doctoral student of chemical engineering at UM and co-lead author of the study.
This research was funded by the National Science Foundation Center for Complex Particle Systems and the American Chemical Society Petroleum Research Fund. The work was published in Chem and Bio Engineering, April 2025.