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

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.