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. 2026 Sep 22;16:1968526. doi: 10.3389/fcimb.2026.1968526

Figure 2.

Infographic with four sections: top left explains liquid nebulization using aerosols with stabilizers, top right describes dry powder spray-drying and its performance metrics, bottom left illustrates deep lung deposition in bronchioles and alveoli, and bottom right shows phage biofilm-targeting mechanisms including binding, degradation, and lysis for enhanced pulmonary delivery. Key attributes at the bottom include formulation stability, aerosol performance, particle size control, storage stability, batch consistency, potency, and safety.

Formulation engineering strategies for pulmonary phage delivery. Four panels summarize the strategies covered in this chapter. (Top-left, purple) Liquid nebulization generates 1–5 μm aerosol droplets, protected by lactose, trehalose, and gelatin, with leucine as a dispersibility enhancer; shear, thermal, and air–liquid interfacial stresses (red dashed lines) are the principal activity-loss factors, monitored by post-nebulization viable titer. (Top-right, blue) Spray-drying—an alternative, non-sequential route—embeds phages with the same excipients into dry powders, evaluated by emitted dose (ED), fine particle fraction (FPF), and mass median aerodynamic diameter (MMAD). (Bottom-left, green) Deep deposition in bronchioles and alveoli. (Bottom-right, orange) Biofilm targeting: phage polysaccharide depolymerases degrade the EPS matrix, DNase degrades extracellular DNA, and phages lyse entrapped bacteria. The bottom strip lists seven translational quality attributes—viable titer, ED, FPF, MMAD, storage stability, endotoxin, and batch potency—linking the two routes to biofilm penetration.