Liposome-entrapped ampicillin in the treatment of experimental murine listeriosis and salmonellosis

Fattal, Elias; Rojas, José Luis Gonzales; Youssef, Mohammad; Couvreur, Patrick; Andremont, Antoine

doi:10.1128/aac.35.4.770

Cited by 46 publications

(26 citation statements)

References 9 publications

(13 reference statements)

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“…Therefore, the intracellular clearance of Salmonella, mainly in macrophages, requires novel therapeutic strategies. In this regard, liposomal and polymeric nanocarriers have been investigated (4,7). Encapsulating drugs within nanoparticles has the potential to reduce toxicity by providing slow, sustained release and to enhance delivery to the intracellular compartments where the bacteria reside.…”

mentioning

confidence: 99%

In Vitro Trafficking and Efficacy of Core-Shell Nanostructures for Treating Intracellular Salmonella Infections

Ranjan¹,

Pothayee

Seleem³

et al. 2009

Antimicrob Agents Chemother

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Nanostructures encapsulating gentamicin and having either amphiphilic (N1) or hydrophilic (N2) surfaces were designed. Flow cytometry and confocal microscopy studies demonstrated a higher rate of uptake for amphiphilic surfaces. A majority of N1 were localized in the cytoplasm, whereas N2 colocalized with the endosomes/lysosomes. Colocalization was not observed between nanostructures and intracellular Salmonella bacteria. However, significant in vitro reductions in bacterial counts (0.44 log 10 ) were observed after incubation with N1, suggesting that the surface property of the nanostructure influences intracellular bacterial clearance.Intracellular pathogens like Salmonella have developed various mechanisms to evade host defenses, and they can establish chronic infections. Aminoglycosides comprise a group of antibiotics that exhibit antimicrobial activity against gram-positive and gram-negative intracellular bacteria. The antimicrobial activities of aminoglycosides are concentration dependent (3). In spite of their efficacy against pathogens in vitro, clinical uses of aminoglycosides are limited by their inability to transport through cell membranes and reduced intracellular drug accumulation, leading to poor bacterial clearance. In addition, repeated administration of aminoglycosides can lead to druginduced ototoxicity and nephrotoxicity (5, 11). Therefore, the intracellular clearance of Salmonella, mainly in macrophages, requires novel therapeutic strategies. In this regard, liposomal and polymeric nanocarriers have been investigated (4, 7). Encapsulating drugs within nanoparticles has the potential to reduce toxicity by providing slow, sustained release and to enhance delivery to the intracellular compartments where the bacteria reside. To improve the transport of antimicrobials into macrophages, it is important that the mechanism(s) of uptake and fate(s) of nanoparticle drug carriers inside the cells be understood.Pluronic triblock copolymers comprised of poly(ethylene oxide) (PEO) terminal blocks with a poly(propylene oxide) (PPO) central block (i.e., PEO-b-PPO-b-PEO) are currently being evaluated for chemotherapy of multidrug-resistant tumors (2). The PPO segments are more hydrophobic than the water-soluble PEO blocks, and this results in increased incorporation into cells. In this study, we designed and synthesized core-shell nanostructures with PEO-b-PPO-b-PEO shells, as described previously (15), and cores containing gentamicin complexed with polyacrylate anions (PAA). A solution of fluorescein-gentamicin (1 ml, 8.8 mg gentamicin) was added to 4 ml of gentamicin sulfate solution (10 mg ml Ϫ1 gentamicin sulfate, 30 mg gentamicin, ϳ3.5 ϫ 10 Ϫ4 eq of cations) to prepare the labeled drug mixture for incorporation into the nanostructures. To fabricate the nanostructured complexes, a hydrophilic PAA-ϩ Na homopolymer and amphiphilic PEO-b-PAA-ϩ Na or PAA-ϩ Na-b-PEO-b-PPO-b-PEO-b-PAA-ϩ Na were codissolved in deionized water, and then fluorescein-or rhodamine-gentamicin-gentamicin sulfate solution was added dr...

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mentioning

confidence: 99%

In Vitro Trafficking and Efficacy of Core-Shell Nanostructures for Treating Intracellular Salmonella Infections

Ranjan¹,

Pothayee

Seleem³

et al. 2009

Antimicrob Agents Chemother

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“…Higher intracellular concentrations of antibiotics enhance the antibacterial activity of phagocytic cells against to intracellular infections when compared to the same free drug dose (Emmen and Storm, 1987;Bas et al, 2000). It was reported that LA and ampicillin- Bakker-Woudenberg et al, 1986;Carryn et al, 2003) or experimental salmonellosis (Fattal et al, 1989), listeriosis (Bakker-Woudenberg et al, 1985, 1988Fattal et al, 1991). On the contrary, it was reported that FA had no good bactericidal activity, nor need higher concentrations to the treatment in the intracellular infections caused by non-typeable Haemophilus influenzae (Ahren et al, 2002), non-typhoid Salmonella (Chiu et al, 1999) or experimental salmonellosis (Fattal et al, 1989).…”

Section: Resultsmentioning

confidence: 99%

Determination of intracellular (neutrophil and monocyte) concentrations of free and liposome encapsulated ampicillin in sheep

Yazar¹,

Baş²,

Yo³

et al. 2006

Vet. Med. - Czech

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In the current study, intracellular (neutrophil and monocyte) concentrations of free and liposome encapsulated ampicillin in sheep were investigated. Free ampicillin (5 mg/kg b.w.) and liposome encapsulated ampicillin (5 mg/kg b.w.) were administered as a bolus intravenous injection to sheep. After the injections, blood samples (5 ml) were collected into tubes from v. jugularis at 10, 30, 60 minutes and 2, 4 and 8 hours. Neutrophils and monocytes were isolated, and lysed in distilled water. Ampicillin concentrations were measured by high performance liquid chromatography. The results indicate that liposome encapsulated ampicillin caused the higher intracellular concentrations within neutrophil (ratio of liposome encapsulated ampicillin/free ampicillin; from 1.393 to 5.416) and monocyte (ratio of liposome encapsulated ampicillin/free ampicillin; from 0.973 to 2.906) cells than free ampicillin, and liposome encapsulated ampicillin existed a longer length of time within neutrophil (4 hours) and monocyte (4 hours) cells than free ampicillin (60 minutes), as well. This formulation may be beneficial, in that the treatment of intracellular infections are caused by sensitive bacteria.

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“…As seen with nanoparticles, ampicillin-containing liposomes concentrate mainly in the spleen and at a lesser extent in the liver. However, liposomes were shown to be less effective for the treatment of acute S. typhimurium-induced samonellosis than PIHCA nanoparticles (108). A single dose of 0.8 mg liposome-bound ampicillin protected 60% of the treated mice in comparison with 100% protection achieved with nanoparticles (106).…”

Section: Salmonellosismentioning

confidence: 99%

“…Different carriers of ampicillin have been developed in order to increase the antibiotic availability at the intracellular sites where the bacteria reside. Distribution studies in uninfected mice showed that when ampicillin was administered intravenously entrapped into liposomes, it quickly concentrated in the liver and mainly in the spleen (108). Moreover, the efficacy of liposomes and free antibiotic were assessed in Listeria-infected mice.…”

Section: Listeriosismentioning

confidence: 99%

Drug delivery systems for potential treatment of intracellular bacterial infections

Imbuluzqueta

Gamazo²,

Ariza³

et al. 2010

Front Biosci

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Liposome-entrapped ampicillin in the treatment of experimental murine listeriosis and salmonellosis

Cited by 46 publications

References 9 publications

In Vitro Trafficking and Efficacy of Core-Shell Nanostructures for Treating Intracellular Salmonella Infections

In Vitro Trafficking and Efficacy of Core-Shell Nanostructures for Treating Intracellular Salmonella Infections

Determination of intracellular (neutrophil and monocyte) concentrations of free and liposome encapsulated ampicillin in sheep

Drug delivery systems for potential treatment of intracellular bacterial infections

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