Introduction
The restricted duration is a fundamental drawback of traditional local anesthetics during postoperative pain from a single injection. Therefore, an injectable local anesthetic that produces repeatable on-demand nerve blocks would be ideal.
Methods
We offer ultrasound-triggered on-demand analgesia consisting of dendritic mesoporous silica nanoparticles (DMSN) carried with ultrasound-sensitive perfluoropentane (PFP) and levobupivacaine (DMSN-bupi-PFP) to achieve repeatable and customizable on-demand local anesthetics.
Results
The vaporization of liquid PFP was triggered by ultrasound irradiation to produce a gas environment. Subsequently, the enhanced cavitation effect could improve the release of levobupivacaine to achieve pain relief under a moderate-intensity ultrasound irradiation. DMSN-bupi-PFP demonstrated a controlled-release pattern and showed a reinforced ultrasonic sensitivity compared to levobupivacaine loaded DMSN (DMSN-bupi). The sustained release of levobupivacaine produced continuous analgesia of more than 9 hours in a model of incision pain, approximately 3 times longer than a single free levobupivacaine injection (3 hours). The external ultrasound irradiation can trigger the release of levobupivacaine repeatedly, resulting in on-demand analgesia. In addition, DMSN-bupi-PFP nanoplatforms for ultrasound-enabled analgesia showed low neurotoxicity and good biocompatibility in vitro and in vivo.
Conclusion
This DMSN-bupi-PFP nanoplatform can be used in pain management by providing long-lasting and on-demand pain alleviation with the help of moderate-intensity ultrasound.
Background
The lack of a satisfactory strategy for postoperative pain management significantly impairs the quality of life for many patients. However, existing nanoplatforms cannot provide a longer duration of nerve blockage with intensity-adjustable characteristics under imaging guidance for clinical applications.
Results
To overcome this challenge, we proposed a biocompatible nanoplatform that enables high-definition ultrasound imaging-guided, intensity-adjustable, and long-lasting analgesia in a postoperative pain management model in awake mice. The nanoplatform was constructed by incorporating perfluoropentane and levobupivacaine with red blood cell membranes decorated liposomes. The fabricated nanoplatform can achieve gas-producing and can finely escape from immune surveillance in vivo to maximize the anesthetic effect. The analgesia effect was assessed from both motor reactions and pain-related histological markers. The findings demonstrated that the duration of intensity-adjustable analgesia in our platform is more than 20 times longer than free levobupivacaine injection with pain relief for around 3 days straight. Moreover, the pain relief was strengthened by repeatable ultrasound irradiation to effectively manage postoperative pain in an intensity-adjustable manner. No apparent systemic and local tissue injury was detected under different treatments.
Conclusion
Our results suggest that nanoplatform can provide an effective strategy for ultrasound imaging-guided intensity-adjustable pain management with prolonged analgesia duration and show considerable transformation prospects.
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