OPTIMIZATION OF PLURONICS-HYALURONIC ACID SYSTEMS: EFFECTS OF MOLECULAR WEIGHT AND IONIC ENVIRONMENT ON GEL STRENGTH AND SOL-GEL TRANSITION TEMPERATURE

Pluronic (PL) are widely utilized in pharmacological and cosmetic applications due to their ability to form gels at physiological temperatures and to modulate bioactives release. For intra-articular applications, research has focused on optimizing gel systems to achieve a less rigid gel structure and enhanced hydrophilicity. This study investigates the impact of incorporating 1% (w/v) hyaluronic acid (HA) with molecular weights of 10 kDa, 200 kDa, and 1500 kDa into Pluronic F127 (20% w/v), F108 (20% w/v), and F68 (20% w/v), in NaCl (154 mM) or MgCl₂ (0.9 mM) solutions of. Rheological parameters assessed included sol-gel transition  temperature (Tsol-gel), consistency, strength, and stability, determined from frequency or temperature sweep and flow curves analysis. The findings revealed that hydrophilic PL, specifically F108 and F68, were more sensitive to increasing HA concentrations, resulting in a decrease in Tsol-gel. With the incorporation of NaCl in F127 and F108 at all HA (200 kDa and 1500 kDa HA) concentrations, exhibited favorable Tsol-gel values for parenteral applications within the range of 24-28 °C. Additionally, the presence of 10 kDa or 200 kDa HA and MgCl₂ significantly enhances gel strength—approximately fourfold ca. 4-fold compared to gels with NaCl. This suggests that Mg²⁺ ions and smaller HA chains promote stronger polymeric interactions by inducing dehydration of the micellar core and enhancing hydrophilic interactions between HA chains and the micellar corona. Conversely, the inclusion of 1500 kDa HA chains tends to reduce gel strength and consistency in the presence of both salts, likely due to the decreased interaction among the supramolecular structures caused by the larger HA chains. Moreover, the addition of 1500 kDa HA results in reduced viscosity at 25 °C for both F127 and F68, suggesting disturbing effects into the structural organization and resistance. In conclusion, F127 and F108, in combination with NaCl and MgCl₂ and HA concentrations of 10 kDa and 200 kDa, demonstrate increased gel strength and consistency. These formulations are promising for drug delivery systems, as they exhibit suitable Tsol-gel transitions for manipulation at environmental and physiological temperatures.

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grant 2023/13068-4 and CNPq 308819/2022-5.