BACKGROUND: The polyethylene glycol/polylactic acid (PEG/PLA) microspheres encapsulated by ropivacaine were prepared by oil in water emulsion solvent evaporation method. In vitro experiments showed that the prepared PEG/PLA microspheres have good pharmacodynamics and in vitro sustained release performance.
OBJECTIVE: To further investigate the in vivo sustained-release properties and histocompatibility of PEG/PLA microspheres encapsulated by ropivacaine.
METHODS: PEG/PLA microspheres encapsulated by ropivacaine were prepared by oil in water O/W emulsion solvent evaporation method. A total of 150 male Wistar rats were provided by Laboratory Animal Center of Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, China and randomly divided into three groups (n=50/group). In the blank control group, PEG/PLA microspheres without ropivacaine encapsulation were implanted into the space surrounding the sciatic nerve on one side. In the common drug group, ropivacaine hydrochloride was injected into the space surrounding the sciatic nerve. In the sustained release drug group, PEG/PLA microspheres encapsulated by ropivacaine were implanted into the same region. The dose of ropivacaine used in the common drug and ropivacaine hydrochloride groups was the same. At 10 and 30 minutes, 1, 3, 5, 7, 10, 15, 30 and 48 hours after drug administration, the sensory block of rat sciatic nerve was evaluated by hot pedal test, the motor block of the sciatic nerve was observed by tail-lifting test, and serum concentration of ropivacaine was analyzed by high performance liquid chromatography. At 1 week after surgery, change in rat body mass was evaluated, and the pathological changes of rat sciatic nerve as well as its surrounding tissue and the important organs such as the heart, liver, lung, kidney, and spleen were observed. This study was approved by the Animal Ethics Committee of Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital.
RESULTS AND CONCLUSION: In the common drug group, sciatic nerve sensory and motor block appeared 30 minutes after drug administration. The sensory block disappeared at 7 hours, and the nerve block disappeared at 10 hours. In the sustained-release drug group, sciatic nerve sensory and motor block occurred 3 hours after drug administration, and the nerve block disappeared at 48 hours. In the common drug group, serum concentration of ropivacaine gradually increased, peaked at 1 hour after drug administration, then rapidly decreased, and was non-detectable at 7 hours. In the sustained-release drug group, serum concentration of ropivacaine was gradually increased to a greater extent at 3 hours, peaked at 10 hours, then gradually decreased, and maintained at a relatively low concentration at 48 hours. In the drug sustained-release group, no respiratory depression, convulsion, asphyxia or death were observed. In addition, incisions healed normally, the increase in body mass was not affected. No obvious structural abnormalities and pathological changes were observed in important organs such as the heart, liver, lung, kidney and spleen. No obvious necrosis, infection and tissue fibrosis were observed in the muscle tissue on the donor side. No obvious pathological changes were observed in the nerve tissue. These results suggest that PEG/PLA microspheres encapsulated by ropivacaine have good sustained-release properties and histocompatibility in vivo.