APRINHA

The project:

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.

CIDETEC’S role in the project:

CIDETEC Nanomedicine will develop and produce a nanoformulation of apramycin using its patented dextran single-chain nanoparticles (KuDa) as excipient to improve the drug bioavailability.