Background and objective Ropivacaine 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. Methods We 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. Results R-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). Conclusion Our 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. Data are available upon reasonable request. All data included in this study are available upon request by contact with the corresponding author.

中文翻译：

---

载罗哌卡因的羟丙基甲壳素热敏水凝胶联合透明质酸：一种可注射的缓释系统，可为大鼠提供长效局部麻醉

背景与目的 盐酸罗哌卡因是临床常用的局麻药。然而，局部注射或连续输注罗哌卡因有几个缺点。因此，重要的是开发一种新的用于局部给药罗哌卡因的控释系统，以达到延长麻醉效果、提高疗效和减少副作用的目的。方法我们开发了注射用羟丙基甲壳素热敏水凝胶（HPCH）与透明质酸（HA）相结合，用于合成载有罗哌卡因（R）的控释系统。然后我们在体外进行了药物释放试验和细胞毒性试验。重要的是，我们通过注射不同浓度的 R-HPCH-HA (7.5, 15, 22.5 mg/mL) 在体内检查了该系统的镇痛作用和生物相容性，大鼠坐骨神经附近的盐酸罗哌卡因（RHCL，7.5 mg/mL）或生理盐水（均为0.5 mL）。结果 R-HPCH-HA 在体内诱导浓度依赖性热感觉阻滞和运动阻滞。在热板试验中，与 RHCL（7.5 mg/mL，5.7±0.8 小时，n=6/组，p<0.05）。它还产生比 RHCL（3.5±0.8 小时，p<0.05）更长时间的运动阻滞（6.8±0.8 小时）。与 RHCL 相比，R-HPCH-HA 引起的细胞毒性较小，如体外细胞活力较高（n = 8/组）所示。结论 我们在坐骨神经阻滞模型中的研究结果表明，可注射的载有罗哌卡因的控释系统可有效延长大鼠的局部镇痛效果，且无明显副作用。可根据合理要求提供数据。本研究中包含的所有数据均可通过与通讯作者联系索取。