A Coarse Grain Molecular Dynamics Study of the Encapsulation of Bupivacaine Enantiomers into Liposomes

M.F. MARTINI; M. PICKHOLZ

Tucumán

Congreso; Reunion Anual de la Sociedad Argentina de Biofísica; 2012

Sociedad Argentina de Biofísica

Bupivacaine (BVC) is a local anesthetic (AL), able to induce a prolonged anesthesia. In this way, it is widely used in both, surgical and post-operative procedures, which benefit from their ability to block the perception and not the motor function. However, the use of this AL can present problems related to its cardiotoxicity. The BVC has a chiral carbon in its chemical structure: its two isomers are dextrobupivacaine [R(+)BVC] and levobupivacaine [S(-)BVC]. Several studies have shown that these isomers show different pharmacological activity, determined by their stereoselectivity. Furthermore, by using drug delivery systems, such liposomes, polymeric micelles, or cyclodextrins is possible to obtain significant improvements in the bioavailability of BVC. The advantages of encapsulating LA in liposomes are the slow drug release, prolonged anesthetic effect and reduced toxicity towards the cardiovascular and central nervous systems [1]. Nowadays, diverse studies have been demonstrated the clinical effectiveness of liposomal formulations containing different anesthetics. In this work, we investigate the encapsulation of neutral BVC into small phospholipid liposomes by Molecular Dynamics (MD) simulations. Because of the size of the system, the study was done at the Coarse Grain level. We have carried out a series of simulations where both enantiomers of neutral BVC were taken into account.