title: Preparation, characterization and in vitro antimicrobial activity of liposomal ceftazidime and cefepime against Pseudomonas aeruginosa strains.
abstract: Pseudomonas aeruginosa is an opportunistic microorganism with the ability to respond to a wide variety of environmental changes, exhibiting a high intrinsic resistance to a number of antimicrobial agents. This low susceptibility to antimicrobial substances is primarily due to the low permeability of its outer membrane, efflux mechanisms and the synthesis of enzymes that promote the degradation of these drugs. Cephalosporins, particularty ceftazidime and cefepime are effective against P. aeruginosa, however, its increasing resistance has limited the usage of these antibiotics. Encapsulating antimicrobial drugs into unilamellar liposomes is an approach that has been investigated in order to overcome microorganism resistance. In this study, antimicrobial activity of liposomal ceftazidime and cefepime against P. aeruginosa ATCC 27853 and P. aeruginosa SPM-1 was compared to that of the free drugs. Liposomal characterization included diameter, encapsulation efficiency and stability. Minimum Inhibitory Concentration (MIC) was determined for free and liposomal forms of both drugs. Minimum Bactericidal Concentration (MBC) was determined at concentrations 1, 2 and 4 times MIC. Average diameter of liposomes was 131.88 nm and encapsulation efficiency for cefepime and ceftazidime were 2.29% end 5.77%, respectively. Improved stability was obtained when liposome formulations were prepared with a 50% molar ratio for cholesterol in relation to the phospholipid. MIC for liposomal antibiotics for both drugs were 50% lower than that of the free drug, demonstrating that liposomal drug delivery systems may contribute to increase the antibacterial activity of these drugs.
authors.affiliation: Laboratório de Tecnologia Farmacêutica e Sistema de Liberação de Fármacos, Faculdade de Farmácia, Universidade Federal de Goias , Goiania, GO , Brasil.
authors.forename: Ieda Maria Sapateiro
authors.initials: IM
authors.lastname: Torres
authors.forename: Etiene Barbosa
authors.initials: EB
authors.lastname: Bento
authors.forename: Larissa da Cunha
authors.initials: Lda C
authors.lastname: Almeida
authors.forename: Luisa Zaiden Carvalho Martins
authors.initials: LZ
authors.lastname: de Sá
authors.forename: Eliana Martins
authors.initials: EM
authors.lastname: Lima
keywords: Pseudomonas aeruginosa; cephalosporins; liposomes
references.citation: Burns. 2006 May;32(3):343-7
references.pmid: 16527415
references.citation: Antimicrob Agents Chemother. 1985 Jan;27(1):137-9
references.pmid: 3872624
references.citation: Int J Pharm. 2006 Jun 6;315(1-2):59-66
references.pmid: 16551496
references.citation: Int J Antimicrob Agents. 1996 May;7(1):9-14
references.pmid: 18611729
references.citation: Biochim Biophys Acta. 2000 Feb 15;1463(2):254-66
references.pmid: 10675504
references.citation: Curr Opin Microbiol. 2005 Oct;8(5):518-24
references.pmid: 16126451
references.citation: Int J Pharm. 2008 May 1;355(1-2):293-8
references.pmid: 18164881
references.citation: Diagn Microbiol Infect Dis. 2006 Sep;56(1):63-8
references.pmid: 16650951
references.citation: Biochem Pharmacol. 2002 Nov 1;64(9):1407-13
references.pmid: 12392822
references.citation: Int J Antimicrob Agents. 2006 Mar;27(3):183-95
references.pmid: 16472990
references.citation: Drug Resist Updat. 2000 Aug;3(4):247-255
references.pmid: 11498392
references.citation: Biochim Biophys Acta. 1999 Aug 5;1428(2-3):334-40
references.pmid: 10434052
references.citation: Antimicrob Agents Chemother. 2006 Jun;50(6):2016-22
references.pmid: 16723560
references.citation: Semin Respir Infect. 2000 Dec;15(4):287-98
references.pmid: 11220411
references.citation: Pharmacol Res. 1995 Jul-Aug;32(1-2):85-7
references.pmid: 8668652
references.citation: Drug Deliv. 2004 Jan-Feb;11(1):33-9
references.pmid: 15168789
references.citation: Int J Antimicrob Agents. 2010 Jun;35(6):553-8
references.pmid: 20219328
references.citation: J Antimicrob Chemother. 2003 Jan;51(1):83-91
references.pmid: 12493791
references.citation: Int J Antimicrob Agents. 2006 Mar;27(3):247-52
references.pmid: 16472992
references.citation: J Antimicrob Chemother. 1998 Jan;41(1):35-41
references.pmid: 9511035
references.citation: J Antimicrob Chemother. 2001 Sep;48(3):333-44
references.pmid: 11532996
references.citation: Am J Med. 2006 Jun;119(6 Suppl 1):S29-36; discussion S62-70
references.pmid: 16735148
references.citation: Int J Pharm. 2009 Feb 9;367(1-2):211-9
references.pmid: 18952159
references.citation: Biochim Biophys Acta. 1998 Sep 23;1374(1-2):9-20
references.pmid: 9814848
references.citation: Pharm Acta Helv. 1995 Jul;70(2):95-111
references.pmid: 7651973
references.citation: J Antimicrob Chemother. 2005 Feb;55(2):269-71
references.pmid: 15590716
references.citation: Postgrad Med. 2005 Jan;117(1):41-8
references.pmid: 15672890
references.citation: Artif Organs. 2003 Jul;27(7):623-30
references.pmid: 12823417