Chemical and Biological Factors in the Control of Brucella and Brucellosis

Gamazo, Carlos; Lecaroz, Maria Concepcion; Prior, Sandra; Vitas, Ana Isabel; Campanero, Miguel Ángel; Irache, Juan M.; Blanco-Prieto, María J.

doi:10.2174/156720106778559038

Cited by 17 publications

(15 citation statements)

References 38 publications

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“…The intracellular location of the pathogen inside phagocytic cells makes its eradication difficult to achieve, since many in vitro active antibiotics fail to reach Brucella-infected cells efficiently, lose their antimicrobial activity in the intracellular environment, or do not persist long enough to produce a therapeutic effect (8). Therefore, the current treatment of human brucellosis requires a combination of antibiotics for long periods of time.…”

mentioning

confidence: 99%

Hydrophobic Gentamicin-Loaded Nanoparticles Are Effective against Brucella melitensis Infection in Mice

Imbuluzqueta

Gamazo

Lana

et al. 2013

Antimicrob Agents Chemother

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The clinical management of human brucellosis is still challenging and demands in vitro active antibiotics capable of targeting the pathogen-harboring intracellular compartments. A sustained release of the antibiotic at the site of infection would make it possible to reduce the number of required doses and thus the treatment-associated toxicity. In this study, a hydrophobically modified gentamicin, gentamicin-AOT [AOT is bis(2-ethylhexyl) sulfosuccinate sodium salt], was either microstructured or encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The efficacy of the formulations developed was studied both in vitro and in vivo. Gentamicin formulations reduced Brucella infection in experimentally infected THP-1 monocytes (>2-log 10 unit reduction) when using clinically relevant concentrations (18 mg/liter). Moreover, in vivo studies demonstrated that gentamicin-AOT-loaded nanoparticles efficiently targeted the drug both to the liver and the spleen and maintained an antibiotic therapeutic concentration for up to 4 days in both organs. This resulted in an improved efficacy of the antibiotic in experimentally infected mice. Thus, while 14 doses of free gentamicin did not alter the course of the infection, only 4 doses of gentamicin-AOTloaded nanoparticles reduced the splenic infection by 3.23 logs and eliminated it from 50% of the infected mice with no evidence of adverse toxic effects. These results strongly suggest that PLGA nanoparticles containing chemically modified hydrophobic gentamicin may be a promising alternative for the treatment of human brucellosis.

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confidence: 99%

Hydrophobic Gentamicin-Loaded Nanoparticles Are Effective against Brucella melitensis Infection in Mice

Imbuluzqueta

Gamazo

Lana

et al. 2013

Antimicrob Agents Chemother

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“…Late endosomal pH of 5 can inactivate or increase the minimum inhibitory concentration of the drug molecule. For example, gentamicin shows a 64‐fold increase in minimum inhibitory concentration at pH 5 (Gamazo et al ., ). Thus, active drug molecules should also be protected from endosomal pH.…”

Section: Challenges In Intracellular Therapymentioning

confidence: 97%

Nanomedicine for intracellular therapy

Ranjan

Pothayee

Seleem

et al. 2012

FEMS Microbiol Lett

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Intracellular pathogens like Salmonella evade host phagocytic killing by various mechanisms. Classical antimicrobial therapy requires multiple dosages and frequent administration of drugs for a long duration. Intracellular delivery of antimicrobials using nanoparticle may effectively devise therapies for bacterial infections. This review will address the mechanisms used by Salmonella to avoid host pathogenic killing, reasons for therapeutic failure and advances in nanoparticle drug delivery technology for efficient intracellular bacterial clearance.

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“…Drugs which end up in the endosomal compartments inside cells can see their biological activity dramatically affected. For example, gentamicin shows a 64-fold increase in MIC at pH 5 in late endosomes [46]. Acidic pH in lysosomes may hamper the activity of some fluoroquinolones [40] but, generally, fluoroquinolones are accumulated by phagocytes without being associated with a specific organelle and show good activity against most sensitive organisms [43].…”

Section: Problematic Intracellular Fate Means Low Intracellular Efficacymentioning

confidence: 99%

Toward an Optimized Treatment of Intracellular Bacterial Infections: Input of Nanoparticulate Drug Delivery Systems

Ladavière

Gref

2015

Nanomedicine (Lond.)

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Intracellular pathogenic bacteria can lead to some of the most life-threatening infections. By evolving a number of ingenious mechanisms, these bacteria have the ability to invade, colonize and survive in the host cells in active or latent forms over prolonged period of time. A variety of nanoparticulate systems have been developed to optimize the delivery of antibiotics. Main advantages of nanoparticulate systems as compared with free drugs are an efficient drug encapsulation, protection from inactivation, targeting infection sites and the possibility to deliver drugs by overcoming cellular barriers. Nevertheless, despite the great progresses in treating intracellular infections using nanoparticulate carriers, some challenges still remain, such as targeting cellular subcompartments with bacteria and delivering synergistic drug combinations. Engineered nanoparticles should allow controlling drug release both inside cells and within the extracellular space before reaching the target cells.

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Chemical and Biological Factors in the Control of Brucella and Brucellosis

Cited by 17 publications

References 38 publications

Hydrophobic Gentamicin-Loaded Nanoparticles Are Effective against Brucella melitensis Infection in Mice

Hydrophobic Gentamicin-Loaded Nanoparticles Are Effective against Brucella melitensis Infection in Mice

Nanomedicine for intracellular therapy

Toward an Optimized Treatment of Intracellular Bacterial Infections: Input of Nanoparticulate Drug Delivery Systems

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