Ropivacaine- and ascorbic acid-loaded thermosensitive hydrogels for pain management

Abstract

Postoperative pain management is one of the significant components of patient care, with the reduction of the risks of complications. However, there is a perceived unmet need for pain management due to both the adverse effects of systemic analgesics and the shortcomings of local anaesthetics. In this study, ropivacaine (RPC)- and ascorbic acid (AA)-loaded hyaluronic acid/Pluronic F127 (HA/F127) composite thermosensitive hydrogels were prepared for sustained analgesia and antioxidant activity. The HA/F127 hydrogels showed temperature-responsive sol–gel behavior with injectable properties at 4° C–20 °C. In addition, the hydrogels showed sustained release of RPC and AA over 72 h with significant radical scavenging activity. In vivo studies indicated that the HA/F127 hydrogels resulted in increased mechanical withdrawal thresholds compared to free RPC, without causing motor impairment, and plasma levels of IL-1β and IL-6 were reduced. In addition, hematological, biochemical, and histological analyses showed acceptable ranges of biocompatibility without evidence of systemic toxicity or adverse local tissue reactions. Thus, the thermosensitive HA/F127 composite hydrogels provided sustained drug release, prolonged analgesic effects, reduced inflammatory responses, and acceptable biocompatibility. These findings indicate that these thermosensitive composite hydrogels may be a promising strategy for local drug delivery in managing postoperative pain and inflammation.