Exploitation of the bilosome platform technology to formulate antibiotics and enhance efficacy of melioidosis treatments
D'Elia, Riccardo V. and Woods, Stuart and Butcher, Wendy and McGahon, Jonathan and Khadke, Swapnil and Perrie, Yvonne and Williamson, E. Diane and Roberts, Craig W. (2019) Exploitation of the bilosome platform technology to formulate antibiotics and enhance efficacy of melioidosis treatments. Journal of Controlled Release, 298. pp. 202-212. ISSN 0168-3659 (https://doi.org/10.1016/j.jconrel.2019.02.002)
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Abstract
Burkholderia pseudomallei is a Gram-negative intracellular bacterium which is recalcitrant to antibiotic therapy. There also is currently no licensed vaccine for this potentially fatal pathogen, further highlighting the requirement for better therapeutics to treat the disease melioidosis. Here we use an oral delivery platform, the bilosome to entrap already- licensed antibiotics. Bilosome-entrapped antibiotics were used to treat mice infected via the aerosol route with B. pseudomallei. When treatment was started by the oral route at 6 h post-infection and continued for 7 days, bilosome levofloxacin and bilosome doxycycline formulations were significantly more efficacious than free antibiotics in terms of survival rates. Additionally, bilosome formulated levofloxacin protected mice from antibiotic and infection induced weight loss following B. pseudomallei infection. The microbiomes of mice treated with levofloxacin were depleted of all phyla with the exception of Firmicutes, but doxycycline treatment had minimal effect on the microbiome. Encapsulation of either drug in bilosomes had no deleterious or clear advantageous effect on microbiome. This indicates that the ability of bilosomes to ameliorate antibiotic induced weight loss is not due to microbiome effects. The bilosome platform not only has potential to reduce adverse effects of orally delivered antimicrobials, but has potential for other therapeutics which may cause detrimental side-effects or require enhanced delivery.
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Item type: Article ID code: 66882 Dates: DateEvent28 March 2019Published4 February 2019Published Online2 February 2019AcceptedSubjects: Medicine > Therapeutics. Pharmacology Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Humanities and Social Sciences (HaSS) > Psychological Sciences and HealthDepositing user: Pure Administrator Date deposited: 11 Feb 2019 10:21 Last modified: 08 Aug 2024 01:38 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/66882