Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection

Wong, Jonathan P.; Yang, Huiming; Blasetti, Karen L.; Schnell, Glen; Conley, John D.; Schofield, L.

doi:10.1016/s0168-3659(03)00358-4

Cited by 131 publications

(83 citation statements)

References 27 publications

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“…In order to overcome the rapid clearance of ciprofloxacin hydrochloride from the lungs, an experimental liposomal formulation was developed. The elimination half-life of liposomally encapsulated ciprofloxacin in experimental animals was 3 h, which resulted in therapeutic efficacy against Francisella tularensis and P. aeruginosa infections (132)(133)(134)(135).…”

Section: Chemistry and Formulationmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.

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Section: Chemistry and Formulationmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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“…For that reason, liposome encapsulation increased the effectiveness of ENR. Studies showed that liposome-encapsulated CPR provided full protection after aerosol inhalation when compared to free CPR in mice in which respiratory infection was induced by F. tularensis 25 …”

Section: Discussionmentioning

confidence: 99%

Cytologic-Enzymologic Diagnosis of Experimental Pneumonia Induced by Klebsiella pneumoniae Serotype II in Rats and Its Treatment with Free and Liposomal Enrofloxacin

Baş¹,

Üney²,

Hadimli³

et al. 2013

Kafkas Univ Vet Fak Derg

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SummaryEnrofloxacin (ENR) rapidly localizes in eukaryotic cells in vitro but does not remain for prolonged periods, thereby reducing the ENR efficacy of defense against intracellular pathogens. Delivery of ENR in a liposome-encapsulated form may enhance its intracellular residence time. In this study, experimental pneumonia was induced in healthy and dexamethasone-treated rats using Klebsiella pneumoniae serotype II. Free and liposome-encapsulated ENR were injected intravenously into the infected animals at a dose of 7.5 mg/kg/day for 5 days. Samples of tissue, plasma and bronchoalveolar lavage (BAL) fluid were obtained at 1, 2, 3 and 4 days and 1, 2, 3 and 4 weeks after the first antibiotic treatment. All of the samples were evaluated cytologically, enzymologically, microbiologically and pathologically. It was determined that cytologic and enzymologic diagnoses of BAL fluid are not meaningful for evaluating the treatment of the experimental pneumonia in rats. However, it was established that the use of ENR in liposomal form at a dose of 7.5 mg/kg for 5 days is more effective than the free form both in the treatment of K. pneumoniae infections and in the prevention of recurrent infections. Liposome-encapsulated antimicrobial agents should provide another choice for antimicrobial therapy in the future, but further investigation must be completed before clinical use. Keywords: Enrofloxacin, Experimental pneumonia, Klebsiella pneumoniae, Liposome, Rat, Treatment Ratlarda Klebsiella pneumoniae Serotip II İle Oluşturulan Deneysel Pnömonilerin Sitolojik-Enzimolojik Teşhisi ve Serbest ve Lipozomlanmış Enrofloksasin İle TedavisiÖzet Enrofloksasin (ENR) in vitro ortamlarda ökaryotik hücrelerde hızla lokalize olur, ancak uzun süre kalamadığı için hücre içi patojenlere karşı onun etkinliği azalır. Lipozomla kapsüle edilmiş formda ENR uygulanması hücre içi ortamlarda kalış zamanını artırabilir. Bu çalışmada, sağlıklı ve deksametazon uygulanmış ratlarda Klebsiella pneumoniae serotip II kullanılarak deneysel pnömoni oluşturuldu. Serbest ve lipozomla kapsüle edilmiş ENR enfekte hayvanlara intravenöz olarak beş gün boyunca 7.5 mg/kg/gün dozda enjekte edildi. İlk antibiyotik uygulamasından sonraki 1, 2, 3, 4. gün ve 1, 2, 3, 4. haftalarda plazma, doku ve bronko-alveolar lavaj (BAL) sıvısı örnekleri alındı. Tüm örnekler sitolojik, enzimolojik, mikrobiyolojik ve patolojik olarak değerlendirildi. Ratlarda deneysel pnömoninin tedavisinin değerlendirilmesinde BAL sıvısının sitolojik ve enzimolojik teşhisinin anlamsız olduğu belirlendi. Ancak, enrofloksasinin beş gün boyunca 7.5 mg/kg dozda lipozomal formda kullanımının hem K. pneumoniae enfeksiyonlarının tedavisinde hem de tekrarlayan enfeksiyonlarının önlenmesinde serbest formdan daha etkili olduğu tespit edildi. Lipozomla kapsüle edilmiş antimikrobiyal ajanlar gelecekte antimikrobiyal tedavide diğer bir seçenek sağlayacaklardır, ancak klinik kullanımdan önce çok sayıda araştırma yapılmalıdır.

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“…Intracellular lethal bacteria, F. tularensis, can be treated via liposomal delivery of ciprofloxacin. In a F. tularensis mouse infection model, this liposomal ciprofloxacin preparation showed significantly better survival than free ciprofloxacin [55]. Another study with liposome encapsulated ciprofloxacin demonstrated enhanced phagocytic functions of macrophage, in turn showing antibacterial activity against S. aureus via two mechanisms: activity due to antibiotic and activity due to increased phagocytic function.…”

Section: Non-targeted Controlled Deliverymentioning

confidence: 90%

Novel drug delivery systems to combat antimicrobial resistance

Mulinti¹,

Hasan²,

Brooks³

2018

Fighting Antimicrobial Resistance

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Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection

Cited by 131 publications

References 27 publications

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Cytologic-Enzymologic Diagnosis of Experimental Pneumonia Induced by Klebsiella pneumoniae Serotype II in Rats and Its Treatment with Free and Liposomal Enrofloxacin

Novel drug delivery systems to combat antimicrobial resistance

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