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Ropivacaine-loaded, hydroxypropyl chitin thermo-sensitive hydrogel combined with hyaluronan: an injectable, sustained-release system for providing long-lasting local anesthesia in rats
  1. Qianqian Qiao1,
  2. Xiangyun Fu1,
  3. Rui Huang1,
  4. Shaoqing Lei1,
  5. Yan Leng1,
  6. Zhigang Liu1,
  7. Zhongyuan Xia1 and
  8. Xulin Jiang2
  1. 1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
  2. 2Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, Hubei, China
  1. Correspondence to Professor Zhongyuan Xia, Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; xiazhongyuan2005{at}aliyun.com; Professor Xulin Jiang, Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, Hubei, China; xljiang{at}whu.edu.cn

Abstract

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.

  • anesthesia
  • local
  • analgesia
  • nerve block
  • pain management
  • animal experimentation

Data availability statement

Data are available upon reasonable request. All data included in this study are available upon request by contact with the corresponding author.

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Data availability statement

Data are available upon reasonable request. All data included in this study are available upon request by contact with the corresponding author.

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Footnotes

  • QQ and XF are joint first authors.

  • ZX and XJ contributed equally.

  • Collaborators QQ, XF, RH, SL, YL, ZL, ZX: Department of Anesthesiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, P.R. China. XJ: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, 299 Bayi Road, Wuhan, 430072, P.R. China.

  • Contributors QQ and XF conducted the experiments, performed the data analysis, and drafted the manuscript. RH, SL, YL, and ZL also performed portions of the experiments and data analysis. ZX and XJ conceived and directed the project, and revised the manuscript. ZX is responsible for the overall content as the guarantor. All authors approved the final version of the manuscript submitted for publication and agree to be accountable for all aspects of the work.

  • Funding This work was supported by the National Natural Science Foundation of China (22175133, 21875168, 21674083).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.