PROLONGED REGIONAL NERVE BLOCKADE - INJECTABLE BIODEGRADABLE BUPIVACAINE POLYESTER MICROSPHERES/

Background: Biodegradable microspheres are a useful method of drug del ivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has chara cterized implantable preparations of local anesthetics in polymer pell ets for prolonged regional anesthesia. In this article, the authors ch aracterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats. Methods: Microspheres were prepared using polylactic-c oglycolic acid polymers loaded with 75% w/w bupivacaine by a solvent e vaporation method. Bupivacaine release from microspheres was determine d in vitro by ultraviolet spectroscopy and scintillation counting, Sen sory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere-suspensions. Results: Depending on the type of microspheres, the dose, and the additive used, mean duration of sciatic nerve block ranged from 10 h to 5.5 days. Incorporation of 0.05% w/w dexamethasone into the microspheres resulted in significant prolongation of block (up to 13-fold), and only preparations that cont ained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not s ubstantially slow bupivacaine release from microspheres in vitro. Conc lusions: Prolonged percutaneous blockade of peripheral nerves is feasi ble, The recovery from blockade is complete, and plasma bupivacaine le vels are far below the range associated with systemic toxicity. The me chanisms underlying the dexamethasone block-prolonging effect are unde r investigation.