Long-Term Synergistic Analgesic Effect Analysis of Co-Delivery Bupivacaine and Dexmedetomidine Loaded by Nano Multilayer Liposome

Abstract

Local anesthetic (LA) is widely used in the treatment of acute or chronic pain. However, due to its short half-life, it is not suitable for long-term effective analgesia and has major toxic and side effects, so its clinical application is limited. Nanoliposomes (NPs) can locally sustain and control drug release, prolonging drug action time and reducing drug side effects. In this study, BUP-DEX-NPs containing bupivacaine (BUP) and dexmedetomidine (DEX) was prepared by multi-layer liposome encapsulation technology, so as to control the orderly release of the two drugs, so as to enhance the analgesic effect and prolong the analgesic time. Microscopical properties were analyzed by particle size, potential and morphology, encapsulation ratio, drug loading and in vitro release performance were determined by High performance liquid chromatography (HPLC), cytotoxicity was tested by CCK8 method, and in vivo analgesic effect was tested by rat plantar incision model. The results showed that BUP-DEX-NPs was a multilayer liposome structure with an average particle size of 209.4±5.8 nm, and low cytotoxicity. BUP encapsulation ratio was 92.15±0.28% and drug loading was 15.85±0.38%. The encapsulation ratio of DEX was 91.36±0.44% and the drug loading was 17.15±0.32%. The drug can be released slowly in vitro and in vivo to prolong the analgesic time, and the synergistic effect of BUP and DEX is better than that of BUP alone. These results indicated that BUP-DEX-NPs had good drug loading performance and long-term analgesic ability. Therefore, the novel double-loading nano-liposomes prepared by multi-layer liposome encapsulation technology in this study show a good application prospect in postoperative long-term synergistic analgesia.