In Vitro Bactericidal Evaluation of a Low Phase Transition Temperature Liposomal Tobramycin Formulation as a Dry Powder Preparation Against Gram Negative and Gram Positive Bacteria

Abstract

In previous studies, delivery of a liquid preparation of encapsulated tobramycin in fluid liposomes, called Fluidosomes, has showed a marked improvement in the bactericidal activity against in-vitro and in-vivo extracellular infections. To examine the possibility of developing aerosol treatment using dehydrated Fluidosomes for the treatment of chronic pulmonary infections, freeze-dried preparations of tobramycin and Fluidosomes were tested against cultures of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burk-holderia cepacia, Escherichia coli and Staphylococcus aureus. Bacterial colonies were enumerated 0, 1, 3, 6 and 16 h after the addition of the antibiotic. Sixteen hours post-treatment, the growth of P. aeruginosa, S. maltophilia, B. cepacia and E. coli in the presence of sub-minimal inhibitory concentrations of tobramycin was significantly lowered respectively by 17 (P < 0.01), 40 (P < 0.001), 47 (P < 0.001), and 50 (P < 0.001) times in comparison with growth in the presence of free antibiotic. No improvement was observed against 5. aureus. Results obtained in this study suggest that: 1) the dehydrated form of liposomal antibiotic maintains the ability to increase penetration of the antibiotic in gram negative bacterial cells; 2) the development of aerosolization methods to administer dehydrated liposomes associated with high concentrations of antibiotic could be a practical and efficient way of treating chronic pulmonary infections caused by resistant bacteria.

Keywords::

• Aerosolization
• Liposomes
• Pseudomonas aeruginosa
• Dry powder