Dataset Information

Evaluation of liposomal ciprofloxacin formulations in a murine model of anthrax.

ABSTRACT: The in vivo efficacy of liposomal encapsulated ciprofloxacin in two formulations, lipoquin and apulmiq, were evaluated against the causative agent of anthrax, Bacillus anthracis. Liposomal encapsulated ciprofloxacin is attractive as a therapy since it allows for once daily dosing and achieves higher concentrations of the antibiotic at the site of initial mucosal entry but lower systemic drug concentrations. The in vivo efficacy of lipoquin and apulmiq delivered by intranasal instillation was studied at different doses and schedules in both a post exposure prophylaxis (PEP) therapy model and in a delayed treatment model of murine inhalational anthrax. In the mouse model of infection, the survival curves for all treatment cohorts differed significantly from the vehicle control. Ciprofloxacin, lipoquin and apulmiq provided a high level of protection (87-90%) after 7 days of therapy when administered within 24 hours of exposure. Reducing therapy to only three days still provided protection of 60-87%, if therapy was provided within 24 hours of exposure. If treatment was initiated 48 hours after exposure the survival rate was reduced to 46-65%. These studies suggest that lipoquin and apulmiq may be attractive therapies as PEP and as part of a treatment cocktail for B. anthracis.

SUBMITTER: Stratilo CW

PROVIDER: S-EPMC6980410 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Evaluation of liposomal ciprofloxacin formulations in a murine model of anthrax.

Stratilo Chad W CW Jager Scott S Crichton Melissa M Blanchard James D JD

PloS one 20200124 1

The in vivo efficacy of liposomal encapsulated ciprofloxacin in two formulations, lipoquin and apulmiq, were evaluated against the causative agent of anthrax, Bacillus anthracis. Liposomal encapsulated ciprofloxacin is attractive as a therapy since it allows for once daily dosing and achieves higher concentrations of the antibiotic at the site of initial mucosal entry but lower systemic drug concentrations. The in vivo efficacy of lipoquin and apulmiq delivered by intranasal instillation was stu ...[more]

PMID: 31978152

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Project description:Colorectal cancer is the second leading cause of cancer-related mortality. Many current therapies rely on chemotherapeutic agents with poor specificity for tumor cells. The clinical success of cisplatin has prompted the research and design of a huge number of metal-based complexes as potential chemotherapeutic agents. In this study, two zinc(II) complexes, [ZnL2] and [ZnL(AcO)], where AcO is acetate and L is an organic compound combining 8-hydroxyquinoline and a benzothiazole moiety, were developed and characterized. Analytical and spectroscopic studies, namely, NMR, FTIR, and UV-Vis allowed us to establish the complexes’ structures, demonstrating the ligand-binding versatility: tetradentate in [ZnL(AcO)] and bidentate in [ZnL2]. Complexes were screened in vitro using murine and human colon cancer cells cultured in 2D and 3D settings. In 2D cells, the IC50 values were <22 µM, while in 3D settings, much higher concentrations were required. [ZnL(AcO)] displayed more suitable antiproliferative properties than [ZnL2] and was chosen for further studies. Moreover, based on the weak selectivity of the zinc-based complex towards cancer cell lines in comparison to the non-tumorigenic cell line, its incorporation in long-blood-circulating liposomes was performed, aiming to improve its targetability. The resultant optimized liposomal nanoformulation presented an I.E. of 76% with a mean size under 130 nm and a neutral surface charge and released the metal complex in a pH-dependent manner. The antiproliferative properties of [ZnL(AcO)] were maintained after liposomal incorporation. Preliminary safety assays were carried out through hemolytic activity that never surpassed 2% for the free and liposomal forms of [ZnL(AcO)]. Finally, in a syngeneic murine colon cancer mouse model, while free [ZnL(AcO)] was not able to impair tumor progression, the respective liposomal nanoformulation was able to reduce the relative tumor volume in the same manner as the positive control 5-fluorouracil but, most importantly, using a dosage that was 3-fold lower. Overall, our results show that liposomes were able to solve the solubility issues of the new metal-based complex and target it to tumor sites.

Project description:The aim of this study was to design and characterize dry powder inhaler formulations of ciprofloxacin and colistin co-loaded liposomes prepared by the ultrasonic spray-freeze-drying (USFD) technique. Liposomal formulations and powder production parameters were optimized to achieve optimal characteristics and in-vitro performance such as encapsulation efficiency (EE), particle size, particle distribution index (PDI), fine particle fraction (FPF), emitted dose (ED) and in vitro antibacterial activity. The formulation (F6) with the mannitol (5% w/v) as the internal lyoprotectant and sucrose (5%, w/v), mannitol (10%, w/v) and leucine (5%, w/w) as the external lyoprotectants/aerosolization enhancers showed an optimal rehydrated EE values of ciprofloxacin and colistin (44.9 ± 0.9% and 47.0 ± 0.6%, respectively) as well as satisfactory aerosol performance (FPF: 45.8 ± 2.2% and 43.6 ± 1.6%, respectively; ED: 97.0 ± 0.5% and 95.0 ± 0.6%, respectively). For the blank liposomes, there was almost no inhibitory effect on the cell proliferation in human lung epithelial A549 cells, showing that the lipid materials used in the liposome formulation is safe for use in pulmonary drug delivery. The cytotoxicity study demonstrated that the optimized liposomal formulation (F6) was not cytotoxic at least at the drug concentrations of colistin 5 ?g/mL and ciprofloxacin 20 ?g/mL. Colistin (2 mg/L) monotherapy showed no antibacterial effect against P. aeruginosa H131300444 and H133880624. Ciprofloxacin (8 mg/L) monotherapy showed moderate bacterial killing for both clinical isolates; however, regrowth was observed in 6 h for P. aeruginosa H133880624. The liposomal formulation displayed superior antibacterial activity against clinical isolates of Pseudomonas aeruginosa H131300444 and P. aeruginosa H133880624 compared to each antibiotic per se. These results demonstrate that the liposomal powder formulation prepared by USFD could potentially be a pulmonary delivery system for antibiotic combination to treat multi-drug resistant Gram-negative lung infections.

Dataset Information

Evaluation of liposomal ciprofloxacin formulations in a murine model of anthrax.

Publications

Evaluation of liposomal ciprofloxacin formulations in a murine model of anthrax.

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