Liposome Encapsulation of Ciprofloxacin Improves Protection against Highly Virulent Francisella tularensis Strain Schu S4

Hamblin, Karleigh A.; Armstrong, Stuart J.; Barnes, Kay B.; Davies, Cheryl M.; Wong, Jonathan P.; Blanchard, James; Harding, Sarah V.; Simpson, Andrew J. H.; Atkins, Helen S.

doi:10.1128/aac.02555-13

Cited by 26 publications

(41 citation statements)

References 27 publications

(37 reference statements)

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“…Encapsulation of antibiotics enhances intracellular uptake and subsequent accumulation to higher therapeutic levels within the intracellular site of infection. Inhaled liposomally encapsulated antibiotics can be a particularly attractive means to provide high sustained concentrations at the sites of action within the respiratory tract, reducing local side effects and systemic exposure and providing more convenient therapy such as once-daily dosing (11) and smaller number of total doses administered for prophylaxis or treatment as shown in this paper and previous studies with CFI (22).…”

Section: Norville Et Almentioning

confidence: 92%

“…It is highly efficacious against several intracellular pathogens, specifically F. tularensis LVS and Schu S4 strains (22) and Y. pestis CO92 strain (K. A. Hamblin, J. D. Blanchard, C. Davies, and S. V. Harding, presented at the 19th Congress of the International Society of Aerosols in Medicine, April 2013, Chapel Hill, NC), with only a single dose being needed to provide full protection against all three pathogens in mouse models of lung infection. This formulation is also very efficacious against the extracellular pathogen Pseudomonas aeruginosa and has completed multiple phase 2 clinical trials for infection in cystic fibrosis and non-cystic fibrosis bronchiectasis patients (41,42).…”

Section: Norville Et Almentioning

confidence: 99%

“…The liposome-encapsulated ciprofloxacin tested in this study, ciprofloxacin for inhalation (CFI), is an advanced formulation specifically designed for inhalation that has already been shown to be highly efficacious in vivo against several intracellular pathogens, specifically F. tularensis LVS and Schu S4 strains (22) and In this study, we report for the first time the evaluation of antibiotic efficacy in an aerosol murine model of Q fever. The efficacy of CFI, ciprofloxacin, and doxycycline as postexposure therapeutics were compared, and single-dose pharmacokinetic profiles were determined.…”

mentioning

confidence: 99%

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Efficacy of Liposome-Encapsulated Ciprofloxacin in a Murine Model of Q Fever

Norville

Hatch

Bewley

et al. 2014

Antimicrob Agents Chemother

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Encapsulation of antibiotics may improve treatment of intracellular infections by prolonging antibiotic release and improving antibiotic uptake into cells. In this study, liposome-encapsulated ciprofloxacin for inhalation (CFI) was evaluated as a postexposure therapeutic for the treatment of Coxiella burnetii, the causative agent of Q fever. Intranasal treatment of male A/Jola (A/J) mice with CFI (50 mg/kg of body weight) once daily for 7 days protected mice against weight loss and clinical signs following an aerosol challenge with C. burnetii. In comparison, mice treated twice daily with oral ciprofloxacin or doxycycline (50 mg/kg) or phosphate-buffered saline (PBS) lost 15 to 20% body weight and exhibited ruffled fur, arched backs, and dehydration. Mice were culled at day 14 postchallenge. The weights and bacterial burdens of organs were determined. Mice treated with CFI exhibited reduced splenomegaly and reduced bacterial numbers in the lungs and spleen compared to mice treated with oral ciprofloxacin or doxycycline. When a single dose of CFI was administered, it provided better protection against body weight loss than 7 days of treatment with oral doxycycline, the current antibiotic of choice to treat Q fever. These data suggest that CFI has potential as a superior antibiotic to treat Q fever.

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Section: Norville Et Almentioning

confidence: 92%

Section: Norville Et Almentioning

confidence: 99%

mentioning

confidence: 99%

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Efficacy of Liposome-Encapsulated Ciprofloxacin in a Murine Model of Q Fever

Norville

Hatch

Bewley

et al. 2014

Antimicrob Agents Chemother

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“…Other potential inhaled bioterrorism threats include anthrax, tularemia, pneumonic plague and Q-fever. Liposomal ciprofloxacin formulations delivered to the lung have shown promising activity in the prevention and treatment of these infections in animal models and are more fully described below [35][36][37].…”

Section: Other Severe Lung Infectionsmentioning

confidence: 99%

“…Without any treatment, inhalational tularemia -infection with F. tularensis -can lead to pneumonic plague-like symptoms and up to 30% mortality [36]. Given the bioterrorism threat of inhalational exposure of this pathogen, there is interest in development of a post-exposure prophylaxis and treatment [36].…”

Section: Other Severe Lung Infectionsmentioning

confidence: 99%

Emerging Opportunities for Inhaled Antibiotic Therapy

Cipolla¹,

Froehlich²,

Gonda³

2015

J Antimicro

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Inhaled antibiotics have become a mainstay of cystic fibrosis (CF) therapy by providing high drug concentrations locally in the lung while minimizing systemic exposure and thus the potential for side effects. In CF, inhaled antibiotics decrease the rate of decline of lung function, improve the quality of life, and reduce the frequency of exacerbations and hospital admissions. However, the burden of therapy remains high in CF. There is an opportunity for more convenient and effective inhaled antibiotics to reduce the disease burden in CF. In contrast, despite the unmet medical need, no inhaled antibiotics are approved for lung infections in a number of other diseases including non-CF bronchiectasis, COPD, melioidosis, pneumonic plague, anthrax, Q fever, tularemia and patients with other infections including non-tuberculous mycobacteria. This review discusses the progress towards achieving that goal in those indications. Additionally, the approved inhaled antibiotics in CF are only available as a fixed dose that is inhaled twice or thrice daily. There is a limited opportunity to personalize therapy to the patient. This review envisions a future scenario where the treatment of lung infections can be optimized to the specific needs of each individual based on the attributes of their infectious agents.

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The Use of Phospholipids to Make Pharmaceutical Form Line Extensions

Hoogevest

Tiemessen

Metselaar

et al. 2021

Euro J Lipid Sci & Tech

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This review describes the use of phospholipid excipients to make Pharmaceutical Form (Dosage Form) Line Extensions of existing drugs as part of a Product Life Cycle Management. Product examples and development candidates, which show the versatility of phospholipids as key excipients in formulations to develop line extension drug products for any administration route by reformulating existing products, are provided. The resulting patented products enable the application of a drug substance for another administration route or show an increased efficacy and/or reduced toxicity of the formulated drug substances, or enable a more convenient use, through reduction of dosing frequency, or adapt a product for regulatory requirements for specific patient populations. Parenteral line extensions for lipophilic drugs using non‐toxic phospholipid‐based solubilising formulations are clearly an alternative to products with solubilising synthetic detergents with the risk for allergic and anaphylactic reactions. This review draws the attention to academic and industrial formulation scientist to consider using phospholipid excipients to reformulate existing products to improve the product properties by an active product life cycle management. Phospholipids are suitable for this purpose because they are biocompatible, biodegradable, non‐toxic, and available at large scale and of pharmaceutical grade. Besides, they are well known to regulatory authorities.

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Liposome Encapsulation of Ciprofloxacin Improves Protection against Highly Virulent Francisella tularensis Strain Schu S4

Cited by 26 publications

References 27 publications

Efficacy of Liposome-Encapsulated Ciprofloxacin in a Murine Model of Q Fever

Efficacy of Liposome-Encapsulated Ciprofloxacin in a Murine Model of Q Fever

Emerging Opportunities for Inhaled Antibiotic Therapy

The Use of Phospholipids to Make Pharmaceutical Form Line Extensions

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