The pharmacodynamics and biocompatibility of ropivacaine loading poly(lactide-co-glycolide) microspheres in mice

Objective To evaluate the efficacy and biocompatibility of a newformulation of ropivacaine loaded in an fatty acid based biodegradable polymer poly (PLGA) when implanted near the sciatic nerve of mice.Methods Twenty-five Kunming mice were implanted with the polymer ropivacaine microspheres(RVP-PLGA-MS) 400 mg/kg and the placebo microspheres(PLAC-PLGA-MS) 400 mg/kg nearby the two sciatic nerves,respectively,which were randomly divided into five grouds of A,B,C,D and E by the implantation time points of 4,10,18,30 and 48 h.The efficacy of the polymer drug combination was determined by measuring the sensory and motor nerve blockade for 48 h.Sensory tests were performed using YLS-6B hot plate,the latency to withdraw the hide paw from the hot plate used as the respond time to the thermal nociception.Motor tests were performed to examine the ability to splay and flex of the hind paw by 4-point scale. The disposed mice were sacrificed one week later,and microscopic examination of the main internal organs and the tissues of implanted sites was performed.Results From 4 to 30 h after implantation,the microspheres in mice,the withdrawal latency of the polymer-ropivacaine microspheres sides were longer in the mice implanted RVP-PLGA-MS than those implanted PLAC-PLGA-MS(P0.05). The 4-point scale of motor tests showed that,at 4 to 30 h,the polymer-ropivacaine microspheres sides were 1-3,the placebo microspheres sides were 1,the sensory and motor nerve blockade recovered after 48 h. Microscopic examination of the implanted sites revealed that only mild infiltration in examined tissues with no pathological findings for internal organs were found.Conclusion Polymer-ropivacaine microspheres can prolong analgesic eficacy of ropivacaine and has good biocompatibility in mice.