ArticlePharmaceutical research2026
Mechanistic Insight into Formation and Release Enhancement of Sulindac-Amino Acid Small-Molecule Hydrogels.
Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeAs research on gels continues to advance, pharmaceutical small-molecule hydrogels have attracted growing interest in formulation development. This study addressed two key questions: whether small-molecule hydrogels could function as an effective solubilization strategy and how to design such hydrogel systems.
methodsSulindac (SUL), a non-steroidal anti-inflammatory drug, is subject to significant limitations in clinical use owing to its low aqueous solubility. Herein, SUL-based small-molecule hydrogel systems were fabricated by simply mixing SUL with biocompatible amino acids in a small volume of deionized water. This study combined theoretical miscibility calculation, molecular dynamics simulation, and experimental verification (preparation, characterization, in vitro solubility and release assessments, etc.) to explore their formation and solubilization mechanisms.
resultsThe formed SUL hydrogels with arginine (ARG) or lysine (LYS) exhibited characteristic three-dimensional network structures and excellent viscoelastic properties. Combined results from characterization analyses and molecular simulations revealed that hydrogel formation was promoted by three factors: favorable miscibility between SUL and ARG/LYS, a dissolution-aggregation equilibrium, and self-assembly driven by intermolecular interactions. Compared to pure SUL, the solubility of SUL in both hydrogels was enhanced more than 500-fold. Additionally, the novel SUL hydrogels demonstrated superior release kinetics and supersaturation capacity, characterized by rapid achievement of peak concentrations and sustained supersaturated release. These performances were attributed to the high-energy state of the hydrogels themselves and the complexation between SUL and ARG/LYS.
conclusionsThis study presents a viable formulation approach for overcoming the poor water solubility of insoluble drugs through the design of small-molecule hydrogel formulations.
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