Analgesic effects of intrathecai injecting 97-9-G4 PLGA sustained-release microspheres into the neuropathic pain rats

Abstract

Objective To study the pain killing effects of intrathecal injection of 97-9-G4 PLGA sustained-release microspheres in the SD rat model of CCI of sciatic nerve. Methods SD rats with intrathecal catheter deployment were randomly divided into 4 groups（n=8）： normal saline group（NS group）, 97-9-G4 group （G group）, 97-9-G4 PLGA sustained-release microspheres group（SRG group） and blank PLGA group（P group）. On the 1 lth day after CCI, the animals in NS group and G group were administered the relevant drugs three times （7 am, 1 pm and 7 pm; i.t.）. Those in SRG group and P group were administered only once （7 am; i.t.）. Paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL） were measured 5 times at the fixed time-point within the period of study. Results The drug entrapment efficiency was 80.4%, drug loading efficiency was 27.78%, and the mean diameter of microspheres was 77 wm. Two peaks of 97-9-G4 were observed in vitro release measurement. About 25.28% was released in the first 30 min and about 71.33% was accumulated released in the period from 30 min to 24 hours. Till 10 days, about 98.3% of 97-9-G4 was accumulated released from the microspheres. In vivo, compared with basic pain threshold, all groups, except sham group exhibited similar values of PWMT and PWTL at the beginning of drug administration. After drug administration, comparedwith NS group, the values of PWMT and PWTL were significantly increased at 8 am; 2 pm and 8 pm（P〈0.05）. At 12 am and 6 pm, there was no significant difference （P〉0.05）. Compared with NS group, the values of PWMT and PWTL in group SRG were significantly increased at all the time points except at 8 am. No significant difference was demonstrated in the values of group P as compared with group NS （P〉0.05）. Conclusion 97-9-G4 PLGA sustained-release microspheres demonstrate good appearance and significant in vitro sustained-release characteristics. In rat CCI models, the microspheres demonstrate good sustained-release effect and efficiently raised the PWMT and PWTL. The sustained-release effect could last more than 12 hours in vivo. Key words: 97-9-G4 ; Poly （lactic-co-glycolic acid） ; Microsphere ; Sustained-release; Intrathecal injection