Inclusion Complex Of S(-) Bupivacaine And 2-hydroxypropyl- β-cyclodextrin: Study Of Morphology And Cytotoxicity

Local anesthetics (LA) belong to a class of pharmacological compounds that attenuate or eliminate pain by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of the nerve impulse. S (-) bupivacaine (S(-) bvc) is a local anesthetic of amino-amide type, widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. This article focuses on the characterization of an inclusion complex of S(-) bvc in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Differential scanning calorimetry, scanning electron microscopy and X-Ray diffraction analysis showed structural changes in the complex. In preliminary toxicity studies, the cell viability tests revealed that the inclusion complex decreased the toxic effect (p<0.001) produced by S(-) bvc. These results suggest that the S(-) bvc:HP-β-CD inclusion complex represents a promising agent for the treatment of regional pain.273207212Araújo, D.R., Cereda, C.M., Brunetto, G.B., Pinto, L.M.A., Santana, M.H., de Paula, E., Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice (2004) Can J Anaesth, 51, pp. 566-572Araújo, D.R., Fraceto, L.F., Braga, A.F.A., de Paula, E., Drug-delivery systems for racemic bupivacaine (S50-R50) and bupivacaine enantiomeric mixture (S75-R25):cyclodextrins complexation effects on sciatic nerve blockade in mice (2005) Rev Bras Anestesiol, 55, pp. 316-328Araújo, D.R., Moraes, C.M., Fraceto, L.F., Braga, A.F.A., de Paula, E., Cyclodextrin-bupivacaine enantiomeric mixture (S75-R25) inclusion complex and intrathecal anesthesia in rats (2006) Rev Bras Anestesiol, 56, pp. 495-506Bibby, D., Davies, N.M., Tueker, I.G., Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems (2000) Int J Pharm, 197, pp. 1-11Covino, B.G., Vassalo, H.G., (1976) Local anesthetics: Mechanisms of action and clinical use, , New York: Grune and Stratton;, 255pFoster, R.H., Markham, A., Levobupivacaine. A review of its pharmacology and use as a local anaesthetic (2000) Drugs, 59, pp. 551-579Grant, G.J., Bansinath, M., Liposomal delivery systems for local anesthetics (2001) Reg Anesth Pain Med, 26, pp. 61-63Gristwood, R.W., Cardiac and CNS toxicity of levobupivacaine: Strengths of evidence for advantage over bupivacaine (2002) Drug Saf, 25, pp. 153-163Hirayama, F., Uekama, K., Cyclodextrin-based controlled drug release system (1999) Adv Drug Deliv Rev, 36, pp. 125-141Huang, Y.F., Pryor, M.E., Mather, L.E., Veering, B.T., Cardiovascular and central nervous system effects of intravenous S-bupivacaine and bupivacaine in sheep (1998) Anesth Analg, 86, pp. 797-804Jong, R.H., (1994) Local anesthetics, , Springfield: CC. Thomas;, 325pKohata, S., Jyodi, K., Ohyoshi, A., Thermal decomposition of cyclodextrins (α -, β-, γ, and modified β-CyD) and of metal-(β-CyD) complex in the solid phase (1993) Thermochim Acta, 217, pp. 187-198Loftsson, T., Brewster, M.E., Pharmaceutical application of Cyclodextrin. 1. Drug solubilization and stabilization (1996) J Pharm Sci, 85, pp. 1017-1025Loukas, Y.L., Vraka, V., Gregoriadis, G., Novel non-acidic formulations of haloperidol complexed with beta-cyclodextrin derivatives (1997) J Pharm Biomed Anal, 16, pp. 263-268Mather, L.E., McCall, P., McNicol, P.L., Bupivacaine enantiomer pharmacokinetics after intercostal neural blockade in liver transplant patients (1995) Anesth Analg, 80, pp. 328-335Michaud, M., Icart, S., Determination of the substitution of hydroxypropylbetadex using fourier transform infrared spectrophotometry (2001) PharmEuropa, 13, pp. 714-716Naidu, N.B., Chowdary, K.P.R., Murthy, K.V.R., Satyanarayana, V., Hayman, A.R., Becket, G., Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems (2004) J Pharm Biomed Anal, 35, pp. 75-86Pinto, L.M.A., Fraceto, L.F., Santana, M.H.A., Pertinhez, T.A., Oyama, S., de Paula, E., Physico-chemical characterization of benzocaine-β-cyclodextrin inclusion complexes (2005) J Pharm Biomed Anal, 39, pp. 956-963Ren, X., Xue, Y., Liu, J., Zhang, K., Zheng, J., Lou, G., Gou, C., Shen, J., A novel cyclodextrin-deri ved tellurium compound with glutathione peroxidase (2002) Chembiochem, 3, pp. 363-365Rose, J.S., Neal, J.M., Kopacz, D.J., Extended-duration analgesia: Update on microspheres and liposomes (2005) Reg Anesth Pain Med, 30, pp. 275-285Strichartz, G.R., Ritchie, J.M., (1987) Local anesthetics: Handbook of experimental pharmacology, , Berlin: Springer-Verlag;, 445pThompson, D.O., Cyclodextrin-enabling excipients: Their present and future use in pharmaceuticals (1997) Crit Rev Ther Drug Carrier Syst, 14, pp. 1-10

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