Antinociceptive effect of bupivacaine encapsulated in poly(D,L)-lactide-co-glycolide microspheres in the acute inflammatory pain model of carrageenin-injected rats.

Encapsulating bupivacaine in poly(D,L)-lactide-coglycolide microspheres may prolong analgesia and diminish systemic toxicity. The antinociceptive effect of bupivacaine-loaded microspheres (1, 2.5, and 5 mg) and plain bupivacaine solutions (1, 2.5, and 5 mg) were compared using the vocalization threshold to paw pressure test (VTPP) in rats. Local anesthetic solutions were injected subcutaneously in the plantar hindpaw. First, the biological inactivity of the vehicle and drug-free microspheres (DFM) was evaluated in normal (n = 8) or carrageenin-injected rats (n = 24). Second, onset of antinociception was evaluated in normal rats (n = 16). We then evaluated the duration of antinociception induced by the different local anesthetic solutions in carrageenin-injected rats (n = 56). Neither the vehicle nor the DFM induced any modification of the VTPP. Onset of antinociception was 5 min for all local anesthetic solutions. Duration of antinociception was 60 min with plain bupivacaine (1 mg) and increased to 90, 120, and 180 min, respectively, for the different doses of bupivacaine-loaded microspheres (1, 2.5, and 5 mg). Larger doses of plain bupivacaine (2.5 and 5 mg) induced systemic toxicity. The encapsulation of bupivacaine in microspheres induced a dose-dependent increase in duration of antinociception as compared with plain bupivacaine.