Supramolecular structure organization and rheological properties modulate the performance of hyaluronic acid-loaded thermosensitive hydrogels as drug-delivery systems

The challenges for developing new pharmaceutical formulations based on natural and synthetic polymers has led to innovation into the design of systems responsive environmental stimuli such as temperature. However, the presence of hydrophilic or hydrophobic molecules, charged groups, or metallic elements can affect their structural behavior and their biopharmaceutical performance This work aims to study and characterize the morphology and structure of polymeric formulations based on Poloxamer (PL) 407 (15 % and 30 % m/v) and its binary with PL 338 (15 % PL 407 + 15 % PL 338) and hyaluronic acid (0.5 % m/v), as drug delivery systems of local anesthetic bupivacaine (0.5 % m/v) and ropivacaine (0.5 % m/v) hydrochloride. For this, it was performed SANS analysis for determination of supramolecular organization and lattice parameters; calorimetry was done to characterize their thermodynamic parameters; rheological analysis flow curve, consistency and adhesion calculation, Maxwell model study. Also, it was performed drug release profiles and calculation of diffusion coefficients. It was identified lamellar structures in PL 407 15 % formulations, and coexistence of cubic and hexagonal phases in PL 407 30 % and binary formulations, however hyaluronic acid, bupivacaine or ropivacaine seem do not affect the type of supramolecular structure. In addition, these additives can modulate viscosity among poloxamers chains, increasing micelle-micelle interactions as it happens in presence of bupivacaine. On the other hand, addition of hyaluronic acid can promote increased structural stabilization by hydrophilic interactions between hyaluronic and micellar corona. It reflects the ability how to control the drug release, as in case of binary system that retained bupivacaine for longer time than other systems, as well it happens when hyaluronic acid is added in PL 407 15 % and PL 407 30 %.