Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation

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 ( $G^{\text{’}}/G^{\text{”}}=1.8$ to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model ( $R^2=0.923$ –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.