title: 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.
authors.affiliation: Institute of Lung Biology and Disease, Helmholtz Zentrum München, D-85764 Neuherberg/Munich, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Semmler-Behnke
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Kreyling
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Shinji
authors.initials: S
authors.lastname: Takenaka
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.forename: Frank S
authors.initials: FS
authors.lastname: Henry
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuda
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D003198:Computer Simulation; D016503:Drug Delivery Systems; D006801:Humans; D007223:Infant; D008168:Lung / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration; D013990:Tidal Volume / Q000502:physiology