63 Liposomal encapsulation of tobramycin: an innovative strategy to enhance treatment of pulmonary infections by <i>Pseudomonas aeruginosa</i>

Abstract Pulmonary infections caused by Pseudomonas aeruginosa remain a major therapeutic challenge, largely due to the difficulty in developing treatments that are both effective and safe. While inhaled tobramycin (TB) is commonly used, its therapeutic efficacy is often limited by rapid clearance and poor penetration into pulmonary mucus. Therefore, the development of advanced drug delivery systems is critical to improving both retention and bioavailability in the lungs. This study aimed to investigate the effectiveness of tobramycin encapsulated in liposomes, with and without PEG (LP-TB and LPPEG-TB), compared to free TB, in treating P. aeruginosa infections in in vitro lung models. The compounds were evaluated for their therapeutic efficacy after 24 h in two cellular lung models (alveolar and bronchial) and an artificial pulmonary mucus (APM) model, all of which were infected with P. aeruginosa. Following assessments of safety and minimum inhibitory concentration (MIC), it was observed that both LP-TB and free TB were rapidly internalised by lung cells. However, LPPEG-TB remained on the cell membrane for a longer period before being internalised. In addition, in the APM model, LPPEG-TB demonstrated a superior ability to traverse the mucus layer compared to LP-TB and free TB. These results suggest that LPPEG-TB holds promise as an effective treatment for P. aeruginosa pulmonary infections, as its enhanced mucus penetration reduces mucociliary clearance, while its extended retention on the cell membrane prior to internalisation promotes sustained antibacterial activity.