1. Exploitation of the bilosome platform technology to formulate antibiotics and enhance efficacy of melioidosis treatments
- Author
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Yvonne Perrie, Craig W. Roberts, Swapnil Khadke, Wendy Butcher, Stuart Woods, Jonathan McGahon, E. Diane Williamson, and Riccardo V. D'Elia
- Subjects
RM ,Burkholderia pseudomallei ,Melioidosis ,medicine.drug_class ,Antibiotics ,Administration, Oral ,Pharmaceutical Science ,Levofloxacin ,02 engineering and technology ,Microbiology ,Bile Acids and Salts ,Mice ,03 medical and health sciences ,Drug Delivery Systems ,medicine ,Animals ,Microbiome ,Adverse effect ,030304 developmental biology ,Doxycycline ,Mice, Inbred BALB C ,0303 health sciences ,biology ,business.industry ,021001 nanoscience & nanotechnology ,Antimicrobial ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,bacteria ,Female ,0210 nano-technology ,business ,medicine.drug - 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.
- Published
- 2019
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