Abstract
This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic. For this purpose, poloxamer- (PL-) based hydrogels were synthesized for evaluating the influence of polymer concentration, hydrophilic-lipophilic balances, and binary system formation on biopharmaceutical properties and pharmacological performance. Transition temperatures were shifted, and rheological analysis revealed a viscoelastic behavior with enhanced elastic/viscous modulus relationship (G′/G” = 1.8 to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model (R2 = 0.923–0.989), indicating the drug diffusion from hydrogels to the medium. RVC-PL hydrogels were potentially biocompatible evoking low cytotoxic effects (in fibroblasts and Schwann cells) and mild/moderate inflammation signs on sciatic nerve nearby histological evaluation. In vivo pharmacological assays demonstrated that PL407 and PL407/338 evoked differential analgesic effects, by prolonging the sensory blockade duration up to ~340 and 250 min., respectively. All those results highlighted PL407 and PL407/338 as promising new strategies for sustaining analgesic effects during the postoperative period.
Highlights
The use of biodegradable materials with high biocompatibility has become one of the main objectives in the biomedical sciences
This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic
We previously reported the development of PL-based binary hydrogels for prolonged infiltrative local anesthesia
Summary
The use of biodegradable materials with high biocompatibility has become one of the main objectives in the biomedical sciences. We previously reported the development of PL-based binary hydrogels for prolonged infiltrative local anesthesia In those studies, the structural analysis evidenced an essential contribution of binary system composition associating their phase organization transitions (from lamellar to hexagonal) and drug release modulation, which were differential for obtaining enhanced sustained drug release [6, 7]. The structural analysis evidenced an essential contribution of binary system composition associating their phase organization transitions (from lamellar to hexagonal) and drug release modulation, which were differential for obtaining enhanced sustained drug release [6, 7] Both studies were designed for in situ administration, being necessary a more detailed biopharmaceutical evaluation focused on the design of PL binary systems, highlighting differences on hydrophilic-lipophilic balances, polymer final concentration, and molecular weight, as well as their impacts on regional nerve blocks and in vitro/in vivo biocompatibility. We developed RVC-loaded PL407 and PL338 PL-based binary hydrogels, considering PL remarkable differences on physicochemical properties, by evaluating the micellization process thermodynamic parameters, rheological features, drug release mechanisms and, the pharmacological effects and biocompatibility in the sciatic nerve blockade model, looking forward to their application for sustained regional anesthesia and postoperative pain management
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