Local neurotoxicity and myotoxicity evaluation of cyclodextrin complexes of bupivacaine and ropivacaine.

Background: Bupivacaine (BVC) and ropivacaine (RVC) are local anesthetics widely used in surgical procedures. In previous studies, inclusion complexes of BVC or RVC in hydroxypropyl-β-cyclodextrin (HP-β-CD) increased differential nervous blockade, compared to the plain anesthetic solutions. In this study we evaluated the local neural and muscular toxicity of these new formulations containing 0.5% BVC or RVC complexed with HP-β-CD (BVC(HP-β-CD) and RVC(HP-β-CD)).

Methods: Schwann cell viability was assessed by determination of mitochondrial dehydrogenase activity, and histopathological evaluation of the rat sciatic nerve was used to identify local neurotoxic effects (48 hours and 7 days after the treatments). Evaluations of serum creatine kinase levels and the histopathology of rat gastrocnemius muscle (48 hours after treatment) were also performed.

Results: Schwann cell toxicity evaluations revealed no significant differences between complexed and plain local anesthetic formulations. However, use of the complexed local anesthetics reduced serum creatine kinase levels 5.5-fold, relative to the plain formulations. The differences were significant at P < 0.05 (BVC) and P < 0.01 (RVC). The histopathological muscle evaluation showed that differences between groups treated with local anesthetics (BVC or RVC) and their respective complexed formulations (BVC(HP-β-CD) or RVC(HP-β-CD)) were significant (P < 0.05).

Conclusions: We concluded that the new formulations presented a lower myotoxicity and a similar cytotoxic effect when compared to plain local anesthetic solutions.