Prolongation of Intrathecal and Sciatic Nerve Blocks Using a Complex of Levobupivacaine with Maltosyl-β-Cyclodextrin in Rats

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. 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. 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. The complex of levobupivacaine with G2-beta-CD prolonged the anesthetic effect of levobupivacaine in both intrathecal and sciatic nerve blocks in rats.