Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection
Abstract
The effect of liposome delivery on the controlled release and therapeutic efficacy of ciprofloxacin against intracellular Francisella tularensis infection in vivo was evaluated in this study. Ciprofloxacin was encapsulated in small unilamellar vesicles by a remote loading procedure using an ammonium sulfate gradient. This procedure produced uniform sized liposomes (100 nm) with an entrapment rate of 90+/-3.5%. Following administration of unencapsulated or liposome-encapsulated ciprofloxacin by intravenous injection or aerosol inhalation, levels of ciprofloxacin in sera, lungs, liver and spleen were determined using 14C-ciprofloxacin as radiotracer for ciprofloxacin. Intravenous injection of liposome-encapsulated ciprofloxacin resulted in higher serum levels of drug in serum, as well as increased drug retention in lungs, liver and spleen, compared to that of free encapsulated drug. Aerosol administration of liposome-encapsulated ciprofloxacin by jet nebulization resulted in significantly higher drug levels and prolonged drug retention in the lower respiratory tract compared to the free drug. Aerosol inhalation of liposome-encapsulated ciprofloxacin, given either prophylactically or therapeutically, provided complete protection to mice against a pulmonary lethal infection model of F. tularensis. In contrast, ciprofloxacin given in its free form, was ineffective. These results suggest that liposome encapsulation of ciprofloxacin enhances drug delivery to the primary site of infection and results in increasing therapeutic efficacy against F. tularensis.
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The half-life of liposome-encapsulated ciprofloxacin in mouse lungs was about double that of the free drug (~3 h versus ~1.5 h).
“The half-life of the liposome-encapsulated drug in mouse lungs was about double that of the free drug (~3 h versus ~1.5 h).”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [33]
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- Authors
- Wong, J. P., Yang, H., Blasetti, K. L., Schnell, G., Conley, J., & Schofield, L. N.
- Affiliations
- Defence Research and Development Canada (CA)
- Corresponding author
- Wong, Jonathan P.
- ORCID
- Wong, Jonathan P.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 92
- Issue
- 3
- Pages
- 265-273
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2051354982
- Cited by
- 153
- References
- 31
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 3 · 2022: 10 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 16 · 2013: 9 · 2012: 7
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacillus and Francisella bacterial research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- liposome encapsulation, ciprofloxacin, Francisella tularensis, tularemia, aerosol drug delivery, jet nebulization, remote loading, controlled drug release, intracellular infection, pulmonary infection, drug retention, prophylaxis, treatment efficacy
- MeSH terms
- Animals, Anti-Infective Agents, Ciprofloxacin, Delayed-Action Preparations, Disease Models, Animal, Female, Francisella tularensis, Injections, Intravenous, Liposomes, Liver, Lung, Mice, Inbred BALB C, Spleen, Tissue Distribution, Tularemia, Survival Rate, Mice
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