Intensity-adjustable pain management with prolonged duration based on phase-transitional nanoparticles-assisted ultrasound imaging-guided nerve blockade.

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.

Artificial nano-red blood cells nanoplatform with lysosomal escape capability for ultrasound imaging-guided on-demand pain management.

Postoperative pain management would benefit significantly from an anesthetic that could take effect in an on-demand manner. An ultrasound would be an appropriate tool for such nanoplatform because it is widely used in clinical settings for ultrasound-guided anesthesia. Herein, we report a nanoplatform for postoperative on-demand pain management that can effectively enhance their analgesic time while providing ultrasonic imaging. Levobupivacaine and perfluoropentane were put into dendritic mesoporous silica and covered with red blood cell membranes to make the pain relief last longer in living organisms. The generated nanoplatform with gas-producing capability is ultrasonic responsive and can finely escape from the lysosomal in cells under ultrasound irradiation, maximizing the anesthetic effect with minimal toxicity. Using an incision pain model in vivo, levobupivacaine's sustained and controlled release gives pain reduction for approximately 3 days straight. The duration of pain relief is over 20 times greater than with a single injection of free levobupivacaine. Effective pain management was reached in vivo, and the pain reduction was enhanced by repeated ultrasonic irradiation. There was no detectable systemic or tissue injury under either of the treatments. Thus, our results suggest that nanoplatform with lysosomal escape capability can provide a practical ultrasound imaging-guided on-demand pain management strategy. STATEMENT OF SIGNIFICANCE: On-demand pain management is essential to postoperative patients. However, the traditional on-demand pain management strategy is hampered by the limited tissue penetration depth of near-infrared stimuli and the lack of proper imaging guidance. The proposed research is significant because it provides a nanoplatform for deep penetrated ultrasound controlled pain management under clinical applicable ultrasound imaging guidance. Moreover, the nanoplatform with prolonged retention time and lysosomal escape capability can provide long-term pain alleviation. Therefore, our results suggest that nanoplatform with lysosomal escape capability can provide an effective strategy for ultrasound imaging-guided on-demand pain management.

Moderate-Intensity Ultrasound-Triggered On-Demand Analgesia Nanoplatforms for Postoperative Pain Management.

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.