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Table 5 In vivo studies of radiolabelled aerosol deposition and distribution under neonatal ventilation conditions

From: Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

Study

Model, body weight

Nebulizer type and position

Nebulized substance

Particle size

Ventilation type

Interface

Lung deposition (% of the nominal dose)

Dubus et al. 2005

Healthy macaques, 2.5–2.8 kg

a) MistyNeb (Jet) at inspiratory limb

b) Aeroneb Pro (VM)

(continuous or sync) at Y-piece

99mTc-DTPA

MistyNeb = 4.6 μm

Aeroneb Pro (cont.) = 4.8 μm

Aeroneb Pro (sync) = 2.8 μm

Mechanical ventilation

ET tube (ID = 3 mm)

Mistyneb = 0.5 (0.4—1.3)*

Aeroneb Pro (cont.) = 12.6 (9.6—20.6)*

Aeroneb Pro (sync) = 14.0 (12.2 – 23.7)*

Linner et al. 2014

Healthy newborn piglets, 1.2–2.2 kg

Investigational eFlow nebulizer (VM) at Y-piece

99mTC-labelled Poractant alfa diluted 1:1 with saline

MMAD = 2.5–3.0 μm (GSD = 1.6)

nCPAP (4 cmH2O)

PPV

Mask, prongs, and ET tube (ID = 2.5 or 3 mm)

Mask (nCPAP) = 5 (3 – 13)*

Prongs (nCPAP) = 14 (2 – 40)*

ET tube (PPV) = 45 (25–56)*

Intratracheal instillation = 88 (71–96)*

Réminiac et al. 2016

Healthy macaques, 3.2–3.6 kg

a) Cirrus2 (Jet) at inspiratory limb

b) Aerogen Solo (VM) at inspiratory limb

99mTc-DTPA

Cirrus2 = 4.0 μm

Aerogen Solo = 4.7 μm

HNF (8, 4 and 2 L/min)

Nasal Cannula

Cirrus2, 8 L/min = 0.03 ± 0.03§

Aerogen Solo, 8 L/min = 0.09 ± 0.04§

Aerogen Solo, 4 L/min = 0.49 ± 0.44§

Aerogen Solo, 2 L/min = 0.85 ± 0.57§

Gregory et al. 2019

Healthy macaques, 4.8–6.8 kg

Aerosurf delivery system (prototype) at Y-piece

99mTC-labelled Lucinactant (surfactant)

MMAD = 2.91 μm (GSD = 1.81)

nCPAP (5 cmH2O)

Prongs with Affectair®

7.52 (3.53 – 14.07)#

Nord et al. 2020

Healthy newborn piglets, 1.2–2.2 kg

Customized eFlow nebulizer (VM) at Y-piece

99mTC-labelled, undiluted Poractant alfa

MMD = 3.0 μm

GSD = 1.5

nCPAP (3 cmH2O)

nIPPV (3 + 3 cmH2O)

Prongs

nCPAP = 15.9 ± 11.9§

nIPPV = 21.6 ± 10.0§

Cunha-Goncalves et al. 2020

Healthy newborn piglets, 1.3–2.2 kg (Treated either in supine, lateral decubitus, or prone position)

Customized eFlow nebulizer (VM) at Y-piece

99mTC-labelled, undiluted Poractant alfa

MMD = 3.0 μm

GSD = 1.5

nCPAP (3 cmH2O)

Prongs

Prone (right lung) = 21.0 ± 8.6§

Prone (left lung) = 10.7 ± 11.4§

Supine (right lung) = 10.7 ± 11.4§

Supine (left lung) = 4.5 ± 2.4§

Right side up (right lung) = 3.4 ± 1.0§

Right side up (left lung) = 15.3 ± 13.4§

Left side up (right lung) = 11.2 ± 9.8§

Left side up (left lung) = 1.8 ± 0.7§

  1. VM, vibrating-mesh; 99mTc-DTPA, Technetium-99 m diethylenetriaminepentaacetic acid; MMAD, mass median aerodynamic diameter; GSD, geometric standard deviation; nCPAP, nasal continuous positive airway pressure; HNF, humidified nasal flow; MMD, mass median diameter; nIPPV, nasal intermittent positive pressure ventilation; ET tube, endotracheal tube; ID, internal diameter. *Median (range); § Mean ± SD; # Mean (range)