Preparation and evaluation of liposome with ropivacaine ion-pairing in local pain management

Abstract

Local analgesia is one of the most desirable methods for postoperative pain control, while the existing local anesthetics have a short duration of analgesic effect. Nano-drug carriers have been widely used in various fields and provide an excellent strategy for traditional drugs. Although the existing liposomes for local anesthetics have certain advantages, their instability and complexity of the preparation process still cannot be ignored. Here, we developed novel ropivacaine hydrochloride liposomes with improved stability and sustained release performance by combining ropivacaine hydrochloride with sodium oleate in liposomes via hydrophobic ion-pairing (HIP). The liposomes are easy to prepare, inexpensive, and suitable for mass production. The infrared (IR), particle size, and Zeta potential measurements adequately characterized the complex, which showed a diameter of 81.09 nm and a zeta potential of −83.3 mV. Animal behavioral experiments, including the hot plate test and von Frey fiber test, demonstrated that the liposome system had a prolonged analgesic effect of 2 h versus conventional liposome preparations, consistent with the results of in vitro release experiments. In addition, in vitro cytotoxicity evaluations in RAW264.7 cells and in vivo evaluations revealed the biocompatibility and safety of the ropivacaine-sodium oleate ion-paired liposome (Rop-Ole-Lipo) system as a suitable local anesthetic for local pain management. Our findings provide a new idea for the preparation of local anesthetics.

Keywords:

• Ropivacaine
• ion-pairing
• liposome
• local anesthesia
• long-term

Acknowledgments

The authors thank the excellent technical assistant of TEM from Zhejiang University.

Author contributions

The idea of this study was conceived by X.W. and K.Z.; experiments were designed and performed by P.K., Y.Q., and Y.T. M.H.; P.K. Y.Q. and M.H. analyzed the data. Z.J., Y.Z., H.Z., Y.L., and M.H. contributed to the revision of the article. P.K., Y.Q., and Y.T. wrote the article with contributions and support from all authors. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was funded by the Natural Science Foundation of Fujian Province, China [Grant No. 2019Y9013 and No. 2020J011080].