Background: We used a cyclodextrin-based drug delivery system, consisting of levobupivacaine complexed with maltosyl-beta-cyclodextrin (G2-beta-CD), in spinal and sciatic nerve blocks in rats to investigate prolongation of the local anesthetic effect.
Methods: Rats were assigned to four groups (n = 6 in each) and received intrathecally 30 microL of 1% levobupivacaine complexed with 0 (control), 50, 100, or 200 mM of G2-beta-CD. Muscle tone and tail flick latency were studied after intrathecal administration. Four more groups (n = 6) of rats received a sciatic nerve block with 0.5% or 1% levobupivacaine complexed with either 0 or 100 mM of G2-beta-CD. The time course of changes in proprioception, motor function, and nociception after circumferential subcutaneous administration to the sciatic nerve was examined.
Results: With the intrathecal block, all rats stopped tail movement immediately after injection of the local anesthetic. The mean time to recovery of muscle tone with 1% levobupivacaine complexed with 100 mM (80.0 +/- 8.9 min) and 200 mM (91.7 +/- 7.0 min) of G2-beta-CD was significantly longer than that of the control group (38.3 +/- 3.1 min), but tail flick latency was not prolonged. With the sciatic nerve block, all rats were temporarily immobilized after levobupivacaine injection. The anesthetic effects of 0.5% levobupivacaine with 100 mM of G2-beta-CD were twice as long as those for 0.5% levobupivacaine alone, and those of 1% levobupivacaine with 100 mM of G2-beta-CD were 1.4 times longer than those for 1% levobupivacaine alone.
Conclusions: The complex of levobupivacaine with G2-beta-CD prolonged the anesthetic effect of levobupivacaine in both intrathecal and sciatic nerve blocks in rats.