Dexmedetomidine and levobupivacaine co-loaded, transcriptional transactivator peptide modified nanostructured lipid carriers or lipid–polymer hybrid nanoparticles, which performed better for local anesthetic therapy?

Local anesthetics (LAs) have been widely applied in clinic for regional anesthesia, postoperative analgesia, and management of acute and chronic pain. Nanostructured lipid carriers (NLCs) and lipid–polymer hybrid nanoparticles (LPNs) are reported as good choices for LA therapy. Transactivated transcriptional activator (TAT) was reported as a modifier for the topical delivery of drugs. In the present study, TAT modified, levobupivacaine (LEV) and dexmedetomidine (DEX) co-delivered NLCs (TAT-LEV&DEX-NLCs, T-L&D-N) and LPNs (TAT-LEV&DEX-LPNs, T-L&D-L) were designed and compared for the LA therapy. T-L&D-L exhibited better efficiency in improving the skin permeation, analgesic time, and pain control intensity than T-L&D-N both in vitro and in vivo. On the other side, T-L&D-N also improved the therapeutic effect of drugs to a large extent. These two systems both exhibited superiority in some respects. TAT modified LPNs are more promising platform for the long-term local anesthesia.