Synthesis and swelling studies of modified chitosan smart hydrogels containing alkyl sulfonate anionic pendant groups...

The hydrogel system effectively delivered insulin, demonstrating its potential to overcome challenges associated with conventional injectable insulin therapies. This pioneering platform leverages smart hydrogels, known for their responsiveness to environmental cues such as temperature, pH, ionic strength, and concentration. Among the fabricated hydrogels, the M5 microparticle, characterized by the lowest cross-linking agent concentration (14%) and the highest propane sultone content used during its preparation, exhibited the greatest water uptake and swelling capacity. Swelling studies confirmed that hydrogel swelling behaviour is significantly influenced by both pH and temperature. Increasing pH leads to increased swelling due to electrostatic repulsion between sulfonate groups (SO₃^-). However, a decrease in the swelling rate was observed in alkaline environments after a certain period, attributed to the removal of sulfonate functional groups via the Hoffman elimination reaction. Concurrently, increasing temperature resulted in an elevated swelling rate, which is likely due to the disruption of intramolecular non-covalent bonds, including hydrogen bonds formed between carboxyl and hydroxyl groups within the hydrogel structure. In other words, elevated temperatures enhance swelling by weakening intramolecular non-covalent bonds and increasing the amount of free space within the hydrogel. The effectiveness of this smart hydrogel-based platform was further validated using insulin as a model drug. Studies indicated that the microparticle loading rate increases with increasing insulin concentration in the loading solution, although this increase becomes less pronounced at higher concentrations. A concentration of 10 IU was determined to be optimal for insulin loading. An investigation into the drug release mechanism from the prepared microparticles suggested a perturbed Fickian mechanism for insulin release based on the obtained diffusion profile. The loading efficiency (LE) for M5 microparticles containing suspended insulin was reported to be 66.03%. This system effectively addresses the challenges associated with conventional injectable insulin therapies, offering a promising approach for precise and sustained insulin release in the body. In summary, this study successfully developed a novel, biocompatible, and smart hydrogel for insulin delivery that responds to pH and temperature changes, leading to controlled drug release and potentially improved therapeutic outcomes compared to traditional methods.