Background & Aims
The incorporation of local anesthetics into injectable PLGA microspheres can be useful in providing prolonged spinal anesthesia effects. A new spinal administration in rabbits has been established to research the sustained release of Bupi-PLGA-MS in vivo, and a method to evaluate the spinal anaesthetic effect was set up.
To study the dose-motor response effect of spinal administration of sustained-release PLGA bupivacaine in rabbits.
Methods
Bupivacaine-loaded microspheres and drug-free microspheres 50-150 um in size were devised from poly-(lactic-co-glycolic) acid (PLGA)by using a emulsifying-solvent evaporation method. The effects of bupivacaine and of similar amounts of bupivacaine-loaded microspheres were studied in 18 rabbits as follows: 0.9% sodium chloride, followed by drug-free microspheres, then 2.5 mg of bupivacaine and 2.5mg of bupivacaine -loaded microspheres (Group I; n = 6); 5mg of bupivacaine, then 5 mg of bupivacaine -loaded microspheres (Group II; n = 6); and 10 mg of bupivacaine and 10mg of bupivacaineloaded microspheres (Group III; n = 6). Motor block was evaluated blindly by observation of walking disturbances, using a scale from 0 (free movements) to 3 (total limb paralysis). A period of 3 days elapsed between each injection.
Results
No limitation on movements was observed after 0.9% sodium chloride and drug-free microspheres injection. With 10 mg, both bupivacaine solutions provided complete motor block ,which was significantly more prolonged with bupivacaine-loaded microspheres than bupivacaine. With 5 and 2.5 mg, block intensity was less marked, and block duration was shorter after administration of bupivacaine-loaded microspheres than after bupivacaine.There was no irritation of Bupi-PLGA-MS to the spinal tissues.
Conclusions
Motor blocks resulting from bupivacaine-loaded microspheres are highly influenced by the amount of drug initially released by the polymer.Bupivacaine PLGA microspheres have sustained-release effect in rabbits, They can provide theory basis for the super long-acting local anesthetics.
References
1. Ohri R, Wang JC, Blaskovich PD, et al.Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision?Anesth Analg. 2013,117(3):717-730.
2. Langerman L,Grant GJ,ZakowskiM,et al. Prolongation of epidural anesthesia using a lipid drug carrier with procaine, lidocaine and tetracaine. Anesth Analg ,1992,75:900-905.
3.Estebe JP,Corre PL,Malledant Y,et al. Prolongation of spinal anesthesia with bupivacaine-loaded (DL-Lactide) microspheres. Anesth Anal,1995,81(1):99-103.
4. Estebe JP,Corre PL,Malledant Y,et al. Prolongation of spinal anesthesia with bupivacaine-loaded (DL-Lactide) microspheres. Anesth Anal,1995,81(1):99-103
Presenting Author
Qiang Fu
Poster Authors
qiang fu
MD;PhD;Professor
General hospital of PLA,Beijing,China
Lead Author
Topics
- Treatment/Management: Pharmacology: Non-opioid