Relationship between particle size and lung retention time of intact solid lipid nanoparticle suspensions after...

The relationship between the particle size and lung retention time of inhaled nanocarriers was unclear, and this uncertainty hampered the design of nanocarriers for pulmonary delivery. The debate resulted from a lack of knowledge regarding the integrity of the involved nanocarriers. A distinguishable bioimaging probe which could differentiate between integrated and disintegrated nanocarriers by emitting different signals was introduced to address this problem. The aza-BODIPY structured aggregation-caused quenching (ACQ) probes were promising candidates, because they showed intense fluorescence signals in intact nanocarriers while quenched after the decomposition of nanocarriers. This attribute was called an on-off switch. In this paper, ACQ probes were encapsulated into a solid lipid nanoparticle suspension (SLNS) with different particle sizes (120-480 nm), and the relationship between particle size and lung retention time after pulmonary delivery was investigated in BALB/c mice. The results showed that a larger particle size led to a longer lung retention time. By comparing with the results of a non-water-quenching probe, the SLNS systems were found to be mostly intact in the pulmonary region. These findings will serve as a firm basis for the design and development of nanocarriers for pulmonary delivery.