Injectable Composite Systems of Gellan Gum:Alginate Microparticles in Pluronic Hydrogels for Bioactive Cargo Controlled Delivery: Optimization of Hydrogel Composition based on Rheological Behavior

Due to the high complexity of some treatments, there is a need to develop drug-delivery systems that can release multiple drugs/bioactive agents at different stages of treatment. In this study, a thermoresponsive injectable dual-release system was developed with gellan gum/alginate microparticles (GG:Alg) within a thermoresponsive Pluronic hydrogel composed of a mixture of Pluronic F127 and F68. The increase in F68 ratio and decrease in F127 lead to higher transition temperatures. The addition of the GG:Alg microparticles decreased the transition temperatures with a linear tendency. In Pluronic aqueous solutions (20 wt.%), the F127:F68 ratios of 16:4 and 17:3 (wt.%:wt.%) and the addition of microparticles (up to 15 wt.%) maintained the sol-gel transition temperatures within a suitable range (between 25 degrees C and 37 degrees C). Microparticles did not hinder the injectability of the system in the sol phase. Methylene blue was used as a model drug to evaluate the release mechanisms from microparticles, hydrogel, and composite system. The hydrogel delayed the release of methylene blue from the microparticles. The hydrogel loaded with methylene blue released at a faster rate than the microparticles within the hydrogel, thus demonstrating a dual-release profile.