Tuning Pluronic Hydrogel Properties via Ionic Strength and Hyaluronic Acid for Optimized Rheology and Drug Delivery Performances.

New formulations based on polymeric matrices have demonstrated promising results as drug delivery systems for intra-articular administration. In this study, we propose a five-step approach to guide the selection of the most adequate formulation, considering some features, such as sol-gel transition temperature, mechanical strength, system stability, and drug release performance. As a model, we developed hydrogels composed of Pluronic F68, F108, and F127 at 20% (w/v), combined with hyaluronic acid (HA) of 10, 200, and 1500 kDa at 1% (w/v), along with NaCl (154 mM) and MgCl2 (0.9 mM), to simulate the intra-articular environment. Physicochemical characterization was conducted through rheological analysis, texture profile analysis, dynamic light scattering, and drug release studies. The addition of salts or HA of varying molecular masses influenced the organization of the hydrogel, promoting either greater structural ordering (as observed with MgCl2 and 200 kDa HA) or reduced structuring (as with 1500 kDa HA). Notably, more rigid systems may impair injectability and alter drug release profiles. The incorporation of different HA molecular masses disrupted dense micellar packingparticularly in F127-based hydrogelsaffecting the gel network while promoting either elastic or entangled characteristics. Furthermore, drug release was slowed in systems where both HA and Pluronic formed an entangled network. Overall, the evaluation of these drug carrier systems allowed the identification of PL formulations with optimal mechanical, structural, and release properties, offering improved efficiency for intra-articular drug delivery applications.