Prolonged regional nerve blockade. Injectable biodegradable bupivacaine/polyester microspheres

Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats.

Microspheres were prepared using polylactic-co-glycolic acid polymers loaded with 75% w/w bupivacaine by a solvent evaporation method. Bupivacaine release from microspheres was determined in vitro by ultraviolet spectroscopy and scintillation counting. Sensory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere suspensions.

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 contained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not substantially slow bupivacaine release from microspheres in vitro.

Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.