Coarse Grain Molecular Dynamics Study on the Encapsulation of Bupivacaine Enantiomers in Liposomes

M PICKHOLZ; M.F. MARTINI

SAO PAULO

Congreso; 10th WORLD CONGRESS ON COMPUTATIONAL MECHANICS (WCCM 2012); 2012

WCCM

Bupivacaine is a local anesthetics (LA) that posses a chiral center. The racemic mixture of bupivacaine was one of the most widely used LA, due to its quality of anesthesia and prolonged duration of action, however it presents high toxicity. However, the R-(+) is more toxic than the S-(-) form. Bupivacaine has a big affinity for the cellular membrane because of their amphiphatic nature. In this way, a better understanding of the interaction of each enantiomer with biological membranes could provide insights, for instance, to improve their efficacy and minimize the side effects. In order to be used as chronic pain relief drug, the encapsulation of bupivacaine into liposomes have been proposed. In this work, we investigate the interaction of neutral buvipacaine (BVC) with model membranes by Molecular Dynamics (MD) simulations. We have carried out a series of simulations where both enantiomers of neutral BVC as well as the racemic mixture were taken into account. Simulations for both enantiomers show that the BVCs molecules are essentially found into the hydrophobic tail region. The BVC-R enantioner follows a bimodal distribution while the BVC-S is found, in more uniform distribution, at the bilayer center. Besides, following our previous work, we are carrying out MD simulations of these systems at the Coarse Grain level.