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Research Article

Construction of meloxicam and bupivacaine co-delivery nanosystem based on the pathophysiological environment of surgical injuries for enhanced postoperative analgesia

Mohan Li1, Yumiao He1, Zongran Liu2,4, Xu Ma2,4, Fengrun Sun3, Lijian Pei1, Chao Ma3, Hongju Liu1, Tianjiao Ji2,4( ), Yuguang Huang1( )
Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
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Graphical Abstract

Based on the pathophysiological features of postoperative incision, a poly(lactic-co-glycolic acid) (PLGA)-lipid core–shell nanostructure encapsulating meloxicam and bupivacaine was constructed. The meloxicam was released in a rapid rate to inhibit acute inflammation, and the following sustained drug release behavior enables the analgesia efficacy last for 7 days after surgery.

Abstract

Besides peripheral nerve injury, the acute inflammation is one of the pathological features of tissues after surgery, which exacerbates the postoperative pain, especially in the first 48 h after the surgery. Multimodal analgesia (MMA), such as the combination of non-steroidal anti-inflammatory drugs (NSAIDs) with local anesthetics, has shown enhanced potency compared with the usage of local anesthetics alone. However, rare formulations can provide long-term analgesia at a single dose. Herein, bupivacaine (BUP, a local anesthetic) loading poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPB) were coated with meloxicam (MLX, an NSAID) loading lipid bilayer (LPM), forming a core–shell nanosystem (NPB@LPM) to provide enhanced and long-term analgesia to treat postoperative pain. MLX was encapsulated in the lipid shell, which enabled high dose MLX to be released in the first 48 h after surgery to reduce the acute inflammation induced pain. BUP was encapsulated in the PLGA core to provide a long-term release for the nerve block. This nanosystem provided a 7-day (whole recovery cycle) effective analgesia in the Brennan’s plantar incision rat model. The tissue reactions of NPB@LPM are benign. This work will provide feasible strategies on designing drug delivery systems for postoperative pain management.

Keywords

core–shell nanostructuremultimodal analgesiaco-delivery systempostoperative pain management

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Nano Research
Volume 16 Issue 12,
December 2023
Pages 13301-13308
DOI: 10.1007/s12274-023-6074-3
Cite this article:
Li M, He Y, Liu Z, et al. Construction of meloxicam and bupivacaine co-delivery nanosystem based on the pathophysiological environment of surgical injuries for enhanced postoperative analgesia. Nano Research, 2023, 16(12): 13301-13308. https://doi.org/10.1007/s12274-023-6074-3
Topics:
Drug delivery
Part of a topical collection:
Special issue for the 20th Anniversary of NCNST

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Received: 29 June 2023
Revised: 03 August 2023
Accepted: 07 August 2023
Published: 12 October 2023
© Tsinghua University Press 2023
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