New Inhalation Formulations for Improved Delivery of Antimicrobials
Antimicrobial drug delivery by inhalation has gained increasing popularity over the past decade, with a purpose of resulting in higher drug concentrations in the respiratory tract when compared to oral or parenteral routes of administration, achieving highly efficacious exposures in the treatment of lower respiratory tract infections (LRTI). However, developing inhalation formulations is demanding and requires technologies to overcome a variety of hurdles and limitations. In the treatment of hospitalized patients with acute LRTI, simple nebulization of injectable drugs is used as an “off-label” method for inhalation, resulting in suboptimal delivery due to inefficient penetration to the site of infection and into biofilms. Innovative formulations, including nanoparticles, have therefore been developed to improve drug deposition at the sites of infection, enhance biofilm penetration, and increase the drug exposure in the relevant sites of infection by controlling drug release and clearance. This has been successful for antibiotics targeting Pseudomonas aeruginosa and in the treatment of chronic LRTI. However, to date no powerful inhalation formulations targeting other pathogens and for the treatment of acute LRTI in hospitalized patients has been developed. Here we propose to utilize the latest advancements in formulation technologies to develop five distinct inhalation formulations of apramycin and competitively evaluate their pharmacokinetics, safety, and efficacy in Acinetobacter baumannii animal infection models, providing a case study for other antimicrobials as well.
- Sven Hobbie, University of Zurich, Switzerland (Coordinator)
- Dorothee Winterberg, Fraunhofer Institute for Toxicology and Experimental Medicine, Germany (Partner)
- Iraida Loinaz, CIDETEC, Spain (Partner)
- Frédéric Tewes, INSERM U1070, French National Institute of Health and Medical Research, France (Partner)
- Edgars Liepinsh, Latvian Institute of Organic Synthesis, Latvia (Partner)
- Anna Fureby, RISE Research Institutes of Sweden, Sweden (Partner)
- Per Gerde, Inhalation Sciences Sweden AB, Sweden (Partner)
Our body’s branching airway system that delivers oxygen deep into our lungs presents an effective barrier to protect our lungs from contaminants in the air, such as dust, pollen, and pollutants, but also bacteria and viruses. The same barrier that protects us from inhaling unwanted matter also presents a considerable hurdle in using the human airways as an effective route of drug delivery. A variety of respiratory diseases benefit from inhaling a drug to route its active ingredient directly to its desired location in the human lung, rather than taking a detour through the stomach or blood circulation. Respiratory infections by bacteria, also known as bacterial pneumonia, can turn into life-threating conditions that could more easily be cured with powerful antibiotic inhalations. A complicating factor in the development of inhaled antibiotics is the fact that large amounts of antibiotics need to be applied, of which only a fraction end up at the actual site of infection. Attempts to improve existing inhalation technologies have seen some progress in recent years. The APRINHA project aims to leverage on some of these achievements to study and compare a variety of novel formulation technologies using the new antibiotic apramycin as a promising case study. Apramycin is expected to be perfectly suited for such studies because it belongs to a drug class that has already been shown to be suited for inhalation. The project aims to develop an antibiotic inhalation with high penetration, deposition, retention, and efficacy of drug, so as to more effectively cure pneumonia patients.