The Fate of Albumin Nanoparticles in the ‘Black Box’ of the Lung – in vivo Investigations of Albumin Nanoparticle Localisation into Lung Tissue, Broncheoalveolar Lavage Cells and Fluid 48 hours Post-Inhalation

Arcadia Woods, Aateka Patel, Anna Babin Morgan, Yanira Riffo-Vasquez, Kenneth Bruce, Lea Ann Dailey, Ben Forbes

Albumin nanoparticles, already in clinical use in the injected formulation Abraxane®, are promising candidates for use in drug delivery to the lung. We have demonstrated by using SPECT/CT imaging that albumin nanoparticles can have a long residence time in the lung (>48 h) with negligible secondary organ accumulation. Little is known, however, about their localisation within the lung during this time and what implications this might have for both particle clearance and for applications in pulmonary medicine. To address this, the proportion of In-111 labelled albumin nanoparticles present in bronchoalveolar lavage (BAL) fluid, BAL cells and lung tissue sampled from male BALB/C mice at 4, 24 and 48 h post dosing was quantified. Analysis showed that most In-111 activity was found within the lung tissue between 4 h – 48 h after dosing with albumin nanoparticles (57.9 – 88.6% of In-111 activity present within the lung), and significantly less activity (p<0.05) was present in the lung lining fluid compared to animals administered In-111 labelled albumin solution. Over 48 h, up to 14.3% of In-111 activity was observed in the BAL cellular fraction of nanoparticle-dosed animals. This suggests that phagocytic uptake plays an important role in albumin nanoparticle fate after inhalation. The results of this study, along with data from SPECT/CT imaging, whole body biodistribution studies and in vitro modelling of particle breakdown in lung lining fluid provide an unprecedented insight into the fate of albumin nanoparticles delivered to the lung.

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