Inhalable liposomes: a formulation decision framework linking design variables to pulmonary barriers, aerosol platforms, and critical quality attributes

A structured narrative review examined how vesicle composition, size, charge, surface modification, and aerosolization affect pulmonary delivery and used the findings to construct an operational formulation decision framework. PubMed was searched for English-language publications from 2021 to September 2026, with targeted searches of publisher and regulatory sources. Selection was non-systematic and relevance-based, without a formal risk-of-bias assessment; 62 sources were graded according to a four-level hierarchy. Several framework elements—aerosol stability, PEG-lipid effects, and nucleic acid delivery—rely partly on non-liposomal comparators, requiring confirmation in conventional liposomes. The framework is an eight-step decision matrix linking therapeutic objective, deposition region, dominant barrier, formulation variables, aerosol platform, and verification readouts, applied to four disease contexts. Smaller or PEGylated vesicles may improve mucus transport, but PEGylation can reduce cellular uptake and alter surfactant interactions; nebulization and drying may compromise vesicle integrity. Amikacin liposome inhalation suspension remains the principal clinical precedent. The approach supports hypothesis-driven selection but requires prospective validation.