An injectable mesoporous silica-based analgesic delivery system prolongs the duration of sciatic nerve block in mice with minimal toxicity.

Abstract The major limitation of traditional local anesthetics is the finite duration of a single injection. The present study developed two kinds of novel injectable anesthetic nanocomposites based on mesoporous silica, and evaluated their long-lasting analgesic effect and biosafety. The nanoparticulate carriers, mesoporous silica nanoparticles (MSNs) and mesoporous silica-coated gold nanorods (GNR@MSN), were firstly constructed using the oil-water biphase reaction approach and then ropivacaine (RPC), a local anesthetic, was loaded into the mesoporous carriers by vacuum suction. Transmission electron microscopic images showed the well-ordered mesoporous structure for drug loading. RPC-loaded MSNs and RPC-loaded GNR@MSN exhibited a sustained-release pattern in vitro, and the latter also showed a controlled-release manner triggered by near-infrared (NIR) irradiation. RPC-loaded MSNs and RPC-loaded GNR@MSN caused an initial sensory blockade in mice that lasted for 6 hours, almost 2.5 folds of that from free RPC solution. Furthermore, upon NIR irradiation, the latter induced three additional periods of the blockade. Neither of them showed motor nerve block, which may be due to the sustained release manner. The low myotoxicity and low neurotoxicity of the two nanocomposites were presented both in vitro and in vivo. These results demonstrate the potential of the mesoporous silica-based analgesic nanocomposites in effectively controlling postoperative pain, maybe RPC-loaded MSNs for moderate pain and RPC-loaded GNR@MSN for severe pain. Statement of Significance Adequate postoperative analgesia helps early functional exercise after surgery and accelerates rapid recovery, while uncontrolled postoperative pain probably develops chronic post-surgical pain that impacts the life quality of patients for a long time. However, postoperative pain management is still a challenge. The current treatment drugs are always accompanied by some side effects due to their systemic effect. Opioids have risks of addiction and respiratory depression, and nonsteroidal anti-inflammatory drugs can lead to gastrointestinal reaction. Therefore, the long-lasting local anesthetic formulation with good biocompatibility is the most promising solution to manage post-surgical pain. The present study developed novel injectable anesthetic nanocomposites based on mesoporous silica, providing long-lasting pain relief in mice with minimal toxicity.