KuDa-tob: an Inhaled tobramycin formulation to improve treatment of Pseudomonas aeruginosa chronic lung infections for cystic fibrosis patients
Julie Movellan1, Núria Blanco-Cabra2,3, José María Marimón4, Eduard Torrents2,3, Damien Dupin1, Hans-Jürgen Grande1,5 & Iraida Loinaz1,6
1 CIDETEC, Basque Research and Technology Alliance (BRTA), Parque Científico y Tecnológico de Gipuzkoa, 20014 Donostia-San Sebastián, Spain
2 Bacterial Infections: Antimicrobial Therapies group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
3 Bacterial Infections: Antimicrobial Therapies group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
4 Microbiology Department, Donostia University Hospital – Biodonostia Health Research Institute
Donostia-San Sebastian, Spain.
5 University of the Basque Country (UPV/EHU), Advanced Polymers and Materials: Physics, Chemistry and Technology Department, Donostia-San Sebastian, Spain
6 Kusudama Therapeutics, Parque Científico y Tecnológico de Gipuzkoa, 20014 Donostia-San Sebastián, Spain
Summary
Cystic fibrosis (CF) is characterized by abnormal mucus hydration due to a defective CFTR protein, leading to the production of difficult-to-clear mucus. This results in airflow obstruction, recurrent infections, and respiratory complications. Tobramycin is the first line of antibiotic treatment against chronic infections of Pseudomonas aeruginosa (PA). Administering the complete daily dose of tobramycin in a single inhalation per day may offer advantages over dividing the dose into two sessions, potentially reducing adaptive resistance, and improving treatment adherence and patient quality of life.
KuDa-tob, a nanoformulation of tobramycin and dextran single chain nanoparticles platform (KuDa) as an excipient, was specifically developed to enhance the bioavailability of the antibiotic. The neutralization of the positive charges of the drug facilitates its diffusion through the mucus and biofilm, reaching the bacteria. In vitro studies have shown that KuDa maintains the antibiotic’s efficacy and promotes its penetration into the biofilm.
Freeze-dried KuDa-tob can be reconstituted for nebulization and redispersed easily at high concentrations without affecting the droplets diameter. Nebulization of KuDa-tob to mice showed similar efficacy between KuDa-tob administered once daily double dose compared to tobramycin in solution administered twice a day single dose. These findings confirmed the potential of KuDa-tob as a once-daily treatment for chronic infections caused by PA for CF patients. Further research and evaluation are currently under progress to confirm its clinical effectiveness and safety.