Shruti Sawant, Li Qu & Qi Zhou
Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA
Summary
The growing threat of multidrug-resistant respiratory infections has intensified the need for alternatives to antibiotics. Bacteriophages (phages) are natural viruses that can infect and kill bacteria and are considered potential alternatives to antibiotics. Inhaled phage delivery is a promising route that allows direct access to the infection site in lung airways for localized antibacterial action. However, phages are vulnerable to manufacturing and aerosolization stresses, which can compromise their viability. Moreover, phages can be internalized by the lung epithelial cells, reducing their availability to kill extracellular bacteria like Pseudomonas aeruginosa.
This study investigates phage encapsulation in liposomes as a strategy to protect phages during (i) formulation, (ii) nebulized delivery, and (iii) post-deposition cellular uptake in the lungs. Phage encapsulation was optimized by tuning the liposome surface charge and phage loading titer. Results indicate that hydrophobic interactions play a more critical role than electrostatic interactions in promoting encapsulation, with negative or neutral liposomes exhibiting limited loss in phage viability. Low phage loading titer favors encapsulation and minimize viability loss. Liposomal encapsulation protects phages from shear stress during nebulization and contributes to a higher fine particle fraction. Phage liposomes demonstrate controlled release, thereby limiting uptake by the epithelial cells and prolonging extracellular retention essential for the bacteria P. aeruginosa. Overall, liposome encapsulation represents an effective strategy to improve inhaled phage delivery.