Efficient Nebulization and Pulmonary Biodistribution of Polymeric Nanocarriers in an Acute Lung Injury Preclinical Model

• Published in: Small science 2024-09, Vol.4 (9), p.n/a
• Main Authors: Solé‐Porta, Anna, Areny‐Balagueró, Aina, Camprubí‐Rimblas, Marta, Fernández Fernández, Elena, O’Sullivan, Andrew, Giannoccari, Rossella, MacLoughlin, Ronan, Closa, Daniel, Artigas, Antonio, Roig, Anna
• Format: Article
• Language: English
• Subjects: Aerosols; Biodistribution; Drug delivery systems; Drug dosages; Drug therapy; Efficiency; Growth factors; Health care; inhalation; Inhalers; lung; Lungs; Microscopy; Mortality; nanocarriers; Nanomaterials; poly(lactic‐co‐glycolic acid); Proteins; vibrating mesh nebulizer
• ISSN: 2688-4046; 2688-4046
• DOI: 10.1002/smsc.202400066

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by acute hypoxemic respiratory failure. Pneumonia and sepsis are the most common causes, turning ARDS into a critical public health problem. Despite recent advances in pharmacological strategies, clinical trials have not demonstrated a reduction in ARDS‐associated mortality. This is in part connected to the singularity of the pulmonary physiological barrier, which hampers drug delivery, specifically at distal areas. To this aim, the use of polymeric nanocarriers as a platform for the efficient delivery of therapeutics to the lungs by nebulization is introduced. Herein, poly(lactic‐co‐glycolic acid) (PLGA) nanocapsules (NCs) loaded with human serum albumin, as an inhalable nanotherapeutic are prepared. The production of stable NCs aerosols in the inhalable range is achieved using a commercial device, while the nanocarrier's physicochemical parameters are only minimally altered after nebulization. Importantly, in vivo studies with healthy and acute lung injury animals show that after inhalation, the NCs are homogeneously distributed throughout the lungs, arriving at the distal areas. The NCs are internalized by alveolar type II cells, avoiding macrophage‐mediated lung clearance. These features make the PLGA NCs excellent vehicles for noninvasive pulmonary delivery, facilitating a ready‐to‐be‐used nanomedicine. Poly(lactic‐co‐glycolic acid) nanocapsules (NCs) are investigated as inhalable nanotherapeutics. Stable aerosols can be produced using a commercial nebulizer without any significant alteration of the NCs. In vivo studies with healthy and acute lung injury animals show NCs homogeneously distributed throughout the lungs, arriving at even distal areas. NCs are internalized by alveolar type II cells, avoiding macrophage‐mediated lung clearance.