Nanoparticle delivery in infant lungs

Abstract

The lung surface is an ideal pathway to the bloodstream for nanoparticle-based drug delivery. Thus far, research has focused on the lungs of adults, and little is known about nanoparticle behavior in the immature lungs of infants. Here, using nonlinear dynamical systems analysis and in vivo experimentation in developing animals, we show that nanoparticle deposition in postnatally developing lungs peaks at the end of bulk alveolation. This finding suggests a unique paradigm, consistent with the emerging theory that as alveoli form through secondary septation, alveolar flow becomes chaotic and chaotic mixing kicks in, significantly enhancing particle deposition. This finding has significant implications for the application of nanoparticle-based inhalation therapeutics in young children with immature lungs from birth to~2 y of age.postnatal lung development | inhalation therapy | pulmonary acinus | aerosol transport and deposition | convective mixing

Size-dependent deposition of inhaled nanoparticles in the rat respiratory tract using a new nose-only exposure system

“…The resulting average breathing rate was 0.16 § 0.02 L/min. This is consistent with some values in the literature, including 0.16 L/min for Wistar rats of average mass 217 g (Whalen et al 2006) and a range of 0.15 to 0.17 L/min for Fischer rats of similar weight (Mauderly 1986), but is lower than other estimates, including 0.23 L/min for similar sized Wistar rats (Filho et al 2014), and the experimentally derived allometric relationship in Semmler-Behnke et al (2012), which predicts a value of 0.24 L/min. The design of the head-out plethysmograph used is such that the seal is close fitting around the neck area, which may affect breathing rates, and the operation is such that once calibrated it is extremely unlikely to overestimate the value.…”

“…Aerosols of nano-sized radioactive iridium particles were generated using a spark generator (DNP 4000, Palas, Karlsruhe, Germany) with radioactive iridium electrodes held in custom made electrode holders. Spark generators have been used to successfully generate metallic nanoparticles from a wide range of conductive materials, including iridium (Semmler-Behnke et al 2012). Briefly, primary particles, which for iridium are a few nanometers in diameter, are made by the homogenous nucleation of vapor produced by arcing between two electrodes in an inert argon atmosphere.…”

The Simultaneous Role of an Alveolus as Flow Mixer and Flow Feeder for the Deposition of Inhaled Submicron Particles

“…Third, in the postnatally developing lung, mixing and deposition of submicron particles in the pulmonary acinus must be age dependent. This is because structural change (alveolation) is the major event in postnatal lung development; the newborn human acinus is largely saccular with few alveoli; and hence, few mixer-feeder units, rapid bulk structural alveolation occurs in the first 2-3 years of life [42]. Accordingly, the pattern of deposition of submicron particles in the infant lung is dramatically age dependent, and must be different from that in the fully developed adult lung.…”

Performance Evaluation of an Andersen Cascade Impactor with an Additional Stage for Nanoparticle Sampling

“…Consequently, evaluating the chemical characteristics of these ultrafine nanoparticles is particularly important for an understanding of the impact to general health of airborne particulates that are small enough to enter the human respiratory system. Because a large proportion of nanoparticles penetrate the lung periphery, i.e., the alveolar region, particles deposited in the alveoli are readily transferred to the blood and are then quickly dispersed throughout the human body, including infants (Hinds, 1999;Bolch et al, 2001;Semmler-Behnke et al, 2012). Furthermore, at least one report on the effect that oral exposure to nanoparticles has on the human body, has determined that all kind of nanoparticle behavior in the environment could be issues that should be investigated (Mahler et al, 2012).…”