Ropivacaine-loaded, hydroxypropyl chitin thermo-sensitive hydrogel combined with hyaluronan: an injectable, sustained-release system for providing long-lasting local anesthesia in rats

Abstract

Background and objectiveRopivacaine hydrochloride is a commonly used local anesthetic in clinics. However, local injection or continuous infusion of ropivacaine has been associated with several disadvantages. Accordingly, it is important to develop a new controlled release system for local administration of ropivacaine to achieve a prolong anesthetic effect, improve efficacy, and minimize the side effects.MethodsWe developed injectable hydroxypropyl chitin thermo-sensitive hydrogel (HPCH) combined with hyaluronan (HA), which was used to synthesize a ropivacaine (R)-loaded controlled release system. We then conducted drug release test and cytotoxicity assay in vitro. Importantly, we examined the analgesic effects and biocompatibility of this system in vivo by injecting different concentrations of R-HPCH-HA (7.5, 15, 22.5 mg/mL), ropivacaine hydrochloride (RHCL, 7.5 mg/mL), or saline (all in 0.5 mL) near the sciatic nerve in rats.ResultsR-HPCH-HA induced concentration-dependent thermal-sensory blockade and motor blockade in vivo. In hot plate test, R-HPCH-HA (22.5 mg/mL) induced a significant longer thermal-sensory blockade (17.7±0.7 hours), as compared with RHCL (7.5 mg/mL, 5.7±0.8 hours, n=6/group, p<0.05). It also produced a more prolonged motor blockade (6.8±0.8 hours) than RHCL (3.5±0.8 hours, p<0.05). R-HPCH-HA caused less cytotoxicity than RHCL, as indicated by the higher cell viability in vitro (n=8/group).ConclusionOur findings in a sciatic nerve block model demonstrated that the injectable, ropivacaine-loaded controlled release system effectively prolonged the local analgesic effect in rats without notable side effects.

Effects of Adding Morphine to Periarticular Infiltration Analgesia Combined with Single Dose Epidural Morphine in Total Knee Arthroplasty: A Randomized Controlled Study

“…Currently, multimodal cocktails reported are mixed preparations, consisting mainly of three or four ingredients. As the base ingredient in the cocktails, the amide ropivacaine is a long‐acting local anesthetic agent that elicits nerve block via reversible inhibition of sodium ion influx in nerve fibers, 16 thus improving satisfaction of both patients and surgeons. Ropivacaine is not very lipophilic and does not penetrate the motor fibers of large myelinated nerves, making it more selective for motor nerves 17,18 .…”

Advances in the use of local anesthetic extended-release systems in pain management

“…Qiao et al. ( 2022 ) combined hydroxypropyl chitin thermo-sensitive hydrogel (HPCH) and HA in combination to construct a ropivacaine sustained release system. It takes advantage of the negatively charged property of HA, which shows mutual attraction with positively charged ropivacaine, thus increasing the drug delivery rate.…”