Liposomal delivery of Ropivacaine prepared with dextran sulfate as drug-trapping polymer agent for long-acting anesthesia

The main problem invariably faced by post-operative patients is persistent pain lasting several days which affects their quality of life. Therefore, therapy providing prolonged analgesic effects is required. Rop is a group of local anesthetics offering a safer alternative to non-opioid analgesics. This study aims to develop and optimize Ropivacaine (Rop)-loaded liposome using Dextran Sulfate as a trapping polymer to enable a sustained release effect. Liposomes were composed of hydrogenated soya phosphatidylcholine and cholesterol and prepared by using the thin-film method. Optimization parameters included drug-to-lipid (D/L) ratios of 1:1 and 1:3, and incubation times of 10, 20, and 30 min. The optimized formulation (D/L ratio 1:1 and 10-min incubation) resulted in a particle size of 177.8 ± 3.82 nm, a PDI of 0.193 ± 0.01, zeta potential of −6.89 ± 4.22 mV, and an encapsulation efficiency of 72.14 ± 1.96 %. In vivo pain behavior was assessed in a postoperative mouse model using a hot plate test at 55 °C. The Rop liposome formulation provided effective analgesia, maintaining % Maximum Possible Effect (%MPE) values above 50 % for up to 8 h longer compared to free Rop with rapid onset within 1 h. The effect was sustained for up to 72 h without adverse reactions. The ability of the liposomal formulation to alleviate chronic pain was also demonstrated by the reduced levels of TNF-α and IL-6 in the postoperative mouse model compared to those of free Rop. In conclusion, the use of Dextran Sulfate has successfully improved the long-acting anesthesia effect of Rop-loaded liposomes.