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Liposomes and antibiotics

Shaimaa Ahmed, Suresh B Vepuri, Mahantesh Jadhav, Rahul S Kalhapure, Thirumala Govender
Nano-drug delivery systems have proven to be an efficient formulation tool to overcome the challenges with current antibiotics therapy and resistance. A series of pH-responsive lipid molecules were designed and synthesized for future liposomal formulation as a nano-drug delivery system for vancomycin at the infection site. The structures of these lipids differ from each other in respect of hydrocarbon tails: Lipid1, 2, 3 and 4 have stearic, oleic, linoleic, and linolenic acid hydrocarbon chains, respectively...
March 9, 2017: Cell Biochemistry and Biophysics
Balak Das Kurmi, Pawan Tekchandani, Rishi Paliwal, Shivani Rai Paliwal
BACKGROUND: Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. Present scenario demands a special focus on developing safe medicine with minimize toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, anti-inflammatory, antibiotics, antiviral, anaesthetic, anticancer etc...
February 22, 2017: Current Drug Metabolism
Alejandro Marín-Menéndez, Costanza Montis, Teresa Díaz-Calvo, Davide Carta, Kostas Hatzixanthis, Christopher J Morris, Michael McArthur, Debora Berti
Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes)...
January 25, 2017: Scientific Reports
Karla A G Gusmão, Daniel M Dos Santos, Virgílio M Santos, María Esperanza Cortés, Pablo V M Reis, Vera L Santos, Dorila Piló-Veloso, Rodrigo M Verly, Maria Elena de Lima, Jarbas M Resende
BACKGROUND: The availability of antimicrobial peptides from several different natural sources has opened an avenue for the discovery of new biologically active molecules. To the best of our knowledge, only two peptides isolated from the frog Leptodactylus labyrinthicus, namely pentadactylin and ocellatin-F1, have shown antimicrobial activities. Therefore, in order to explore the antimicrobial potential of this species, we have investigated the biological activities and membrane interactions of three peptides isolated from the anuran skin secretion...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
Sławomir Lewicki, Monika Leśniak, Eugeniusz Krzysztof Machaj, Małgorzata Antos-Bielska, Elżbieta Anna Trafny, Janusz Kocik, Zygmunt Pojda
Liposomes are used for encapsulation of the active compounds in different therapies, with the increasing frequency. The important areas of clinical applications of liposomes are cancer targeted treatment, antibiotic delivery or regenerative medicine. The liposomes can transfer both hydrophilic and hydrophobic compounds and have the lipid bilayer which imitates the cell membrane. Liposomes additionally may extend half-live period of drugs and protect them against the elimination in different ways, such as phagocytosis, enzymatic cleavage or exclusion by detoxification...
January 8, 2017: Journal of Liposome Research
Kristina M Hamill, Lisa S McCoy, Ezequiel Wexselblatt, Jeffrey D Esko, Yitzhak Tor
Polymyxin B is an antibiotic used against multi-resistant gram negative infections, despite observed nephrotoxicity. Here we report the synthesis of functionalized derivatives of polymyxin B and its per-guanidinylated derivative in order to further explore the structural requirements necessary to facilitate uptake of the antibiotic into mammalian cells. We also investigate the possibility of using these novel scaffolds as molecular transporters. At nanomolar concentrations, both are capable of delivering large cargo (>300 kDa) into living cells...
August 1, 2016: Chemical Science
Xiaowei Liu, Zhan Li, Xiaodong Wang, Yujuan Chen, Fengbo Wu, Ke Men, Ting Xu, Yan Luo, Li Yang
Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT...
2016: International Journal of Nanomedicine
José Oñate-Garzón, Marcela Manrique-Moreno, Steven Trier, Chad Leidy, Rodrigo Torres, Edwin Patiño
Antimicrobial peptides are effector molecules of the innate immune system against invading pathogens. The cationic charge in their structures has a strong correlation with antimicrobial activity, being responsible for the initial electrostatic interaction between peptides and the anionic microbial surface. This paper contains evidence that charge modification in the neutral peptide Gm cecropin D-like (WT) improved the antimicrobial activity of the modified peptides. Two cationic peptides derived from WT sequence named as ΔM1 and ΔM2, with net charge of +5 and +9, respectively, showed at least an eightfold increase in their antimicrobial activity in comparison to WT...
March 2017: Journal of Antibiotics
Petra Matouskova, Ivana Marova, Jitka Bokrova, Pavla Benesova
Resistance of microorganisms to antibiotics has increased. The use of natural components with antimicrobial properties can be of great significance to reduce this problem. The presented work is focused on the study of the effect of encapsulation of selected plant and animal antimicrobial substances (herbs, spices, lysozyme and nisin) on their activity and stability. Antimicrobial components were packaged into liposomes and polysaccharide particles (alginate, chitosan and starch). Antimicrobial activity was tested against two Gram-positive (Bacillus subtilis and Micrococcus luteus) and two Gram-negative (Escherichia coli and Serratia marcescens) bacteria...
September 2016: Food Technology and Biotechnology
Pedro Llinares, Isabel Ruiz, Rafael Zaragoza, Ricard Ferrer, Alejandro H Rodríguez, Emilio Maseda, Santiago Grau
BACKGROUND: Although in the past decade the management of invasive fungal infections has improved, a number of controversies persist regarding empirical antifungal treatment in critically-ill hematology patients. AIMS: To identify key clinical knowledge to elaborate a set of recommendations, with a high level of consensus, necessary for the approach to fungal infections in critically-ill hematology patients. METHODS: A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists in fungal invasive infections from six scientific national societies; intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases...
October 2016: Revista Iberoamericana de Micología
Takuya Kaji, Motoki Murai, Hiroaki Itoh, Jyunichiro Yasukawa, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue
Lysocin E (1) is a structurally complex 37-membered depsipeptide comprising 12 amino-acid residues with an N-methylated amide and an ester linkage. Compound 1 binds to menaquinone (MK) in the bacterial membrane to exert its potent bactericidal activity. To decipher the biologically important functionalities within this unique antibiotic, we performed a comprehensive structure-activity relationship (SAR) study by systematically changing the side-chain structures of l-Thr-1, d-Arg-2, N-Me-d-Phe-5, d-Arg-7, l-Glu-8, and d-Trp-10...
November 14, 2016: Chemistry: a European Journal
Jordi Rello, Eleonora Bunsow, Antonio Perez
Bacterial resistance to antibiotics is increasing worldwide, due to the emergence of multidrug-resistant strains. With this panorama, there is a serious danger that we may be entering the 'post-antibiotic era'. Areas covered: We assess why so few new classes of antibiotics have been developed in the past years and discuss a variety of treatments that may be able to replace antimicrobials: monoclonal antibodies, bacteriophages, stem cells and anti-virulence agents such as liposomes. Expert commentary: There are a series of economic, scientific-research and regulatory reasons for the scarcity of new antimicrobials...
December 2016: Expert Review of Clinical Pharmacology
Jin Zhang, Kyle Scoten, Suzana K Straus
Daptomycin is a lipopeptide antibiotic approved for use against Gram-positive organisms, including highly resistant species. A number of studies have suggested that daptomycin kills bacteria by membrane permeabilization and depolarization. Recently a model membrane system consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) in a 1:1 ratio and the ionophore CCCP was proposed as a simple model to investigate the mode of action of daptomycin and resistance mechanisms at a molecular level...
October 14, 2016: ACS Infectious Diseases
Petra Uttlová, Dominik Pinkas, Olga Bechyňková, Radovan Fišer, Jaroslava Svobodová, Gabriela Seydlová
Surfactin, an anionic lipopeptide produced by Bacillus subtilis, is an antimicrobial that targets the cytoplasmic membrane. Nowadays it appears increasingly apparent that the mechanism of resistance against these types of antibiotics consists of target site modification. This prompted us to investigate whether the surfactin non-producing strain B. subtilis 168 changes its membrane composition in response to a sublethal surfactin concentration. Here we show that the exposure of B. subtilis to surfactin at concentrations of 350 and 650 μg/ml (designated as SF350 and SF650, respectively) leads to a concentration-dependent growth arrest followed by regrowth with an altered growth rate...
December 2016: Biochimica et Biophysica Acta
Zhao Wang, Yufan Ma, Hayssam Khalil, Rutao Wang, Tingli Lu, Wen Zhao, Yang Zhang, Jamin Chen, Tao Chen
BACKGROUND: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of bacteria to conventional antibiotics made it imperative to develop new liposome formulations for antibiotics, and investigate the fusion between liposome and bacterium...
2016: International Journal of Nanomedicine
Alberto Oddo, Thomas T Thomsen, Hannah M Britt, Anders Løbner-Olesen, Peter W Thulstrup, John M Sanderson, Paul R Hansen
Bacterial resistance to antibiotic therapy is on the rise and threatens to evolve into a worldwide emergency: alternative solutions to current therapies are urgently needed. Cationic amphipathic peptides are potent membrane-active agents that hold promise as the next-generation therapy for multidrug-resistant infections. The peptides' behavior upon encountering the bacterial cell wall is crucial, and much effort has been dedicated to the investigation and optimization of this amphipathicity-driven interaction...
August 11, 2016: ACS Medicinal Chemistry Letters
Hazem Khalaf, Sravya Sowdamini Nakka, Camilla Sandén, Anna Svärd, Kjell Hultenby, Nikolai Scherbak, Daniel Aili, Torbjörn Bengtsson
BACKGROUND: The complications in healthcare systems associated with antibiotic-resistant microorganisms have resulted in an intense search for new effective antimicrobials. Attractive substances from which novel antibiotics may be developed are the bacteriocins. These naturally occurring peptides are generally considered to be safe and efficient at eliminating pathogenic bacteria. Among specific keystone pathogens in periodontitis, Porphyromonas gingivalis is considered to be the most important pathogen in the development and progression of chronic inflammatory disease...
2016: BMC Microbiology
Hong Jiang, Meimei Xiong, Qiuyan Bi, Ying Wang, Chong Li
Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antibiotic molecules were modified on the surface of carriers as targeting ligands of certain bacteria while more antibiotic molecules were loaded inside the carriers, and thus has the potential to improve the drug concentration at the infection site, enhance efficacy and reduce potential toxicity. In this study, a novel targeted delivery system against methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was constructed with daptomycin, a lipopeptide antibiotic, which can bind to the cell wall of S...
July 2016: Acta Pharmaceutica Sinica. B
Annie H Cheung Lam, Natalie Sandoval, Ritambhara Wadhwa, Janine Gilkes, Thai Q Do, William Ernst, Su-Ming Chiang, Suzanne Kosina, H Howard Xu, Gary Fujii, Edith Porter
BACKGROUND: Healthcare associated infections (HAI) with multidrug-resistant (MDR) bacteria continue to be a global threat, highlighting an urgent need for novel antibiotics. In this study, we assessed the potential of free fatty acids and cholesteryl esters that form part of the innate host defense as novel antibacterial agents for use against MDR bacteria. METHODS: Liposomes of six different phospholipid mixtures were employed as carrier for six different fatty acids and four different cholesteryl esters...
July 8, 2016: BMC Research Notes
H M H N Bandara, M J Herpin, D Kolacny, A Harb, D Romanovicz, H D C Smyth
The challenge of eliminating Pseudomonas aeruginosa infections, such as in cystic fibrosis lungs, remains unchanged due to the rapid development of antibiotic resistance. Poor drug penetration into dense P. aeruginosa biofilms plays a vital role in ineffective clearance of the infection. Thus, the current antibiotic therapy against P. aeruginosa biofilms need to be revisited and alternative antibiofilm strategies need to be invented. Fungal quorum sensing molecule (QSM), farnesol, appears to have detrimental effects on P...
August 1, 2016: Molecular Pharmaceutics
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