Evaluating the Controlled Release Properties of Inhaled Nanoparticles Using Isolated, Perfused, and Ventilated Lung Models

Table 1

Typical examples of pulmonary drug delivery studies employing isolated, perfused, and ventilated lung models.

Organ donor animal	Perfusion system	Ventilation system	Drug/formulation	Formulation application	Analytics	References
Rat	Recirculating flow, 15 mL/min; Krebs-Ringer/Krebs-Henseleit buffer + 4% BSA	Alternating “negative” pressure; tidal volume: ~1 mL, ventilation frequency: 7–28 strokes/min	Fluorescent dyes, labeled dextrans, polypeptides (polyaspartamide, insulin); solution	“Forced solution instillation”	Fluorescence spectroscopy, ELISA	[142–152]
	Recirculating or single-pass flow, 7–11 mL/min; Krebs-Ringer buffer + 4.5% BSA	Alternating “negative” pressure; tidal volume: ~1 mL, ventilation frequency: 70 strokes/min	Budesonide; solution	Instillation	HPLC, liquid scintillation counting	[153]
	Recirculating flow, 5 mL/min; Krebs-Henseleit buffer + 3% BSA	“Positive” pressure inflation; tidal volume: 2, 4 mL, ventilation frequency: 60, 30 strokes/min	Levofloxacin; solution	Nebulization	HPLC	[154]
	Single-pass flow, ~17 mL/min; Krebs-Ringer buffer + 2% BSA	Alternating “negative” pressure; tidal volume: ~1 mL, ventilation frequency: 75 strokes/min	Budesonide, formoterol, terbutaline; powder	Powder aerosolization (DustGun® technology)	LC-MS/MS	[155]
	Recirculating flow, 10–12 mL/min; Krebs-Ringer buffer + 4.5% BSA	Alternating “negative” pressure; tidal volume: ~1 mL, ventilation frequency: 80 strokes/min	Diverse low molecular weight therapeutic agents, labelled dextrans, oligopeptides; solution	Nebulization, instillation (Aeroprobe® technology)	Fluorescence spectroscopy, LC-MS/MS	[156, 157]
Guinea pig	Single-pass flow, 10 mL/min; Krebs-Ringer buffer + 4.5% BSA	Alternating “negative” pressure; tidal volume: ~2 mL, ventilation frequency: 80 strokes/min	Xanthines; solution	Instillation	liquid scintillation counting	[158]
Rabbit	Recirculating flow, 100 mL/min; Krebs-Henseleit buffer (+ 4% hydroxyethyl-amylopectine)	“Positive” pressure inflation; tidal volume: 30 mL, ventilation frequency: 30 strokes/min	Fluorescent dyes, salbutamol, iloprost; solution, nanosuspension	Nebulization, instillation	Fluorescence spectroscopy; HPLC; RIA	[106, 159–161]
	Recirculating flow; Krebs-Ringer buffer + 4.5% BSA	Alternating “negative” pressure	Isoproterenol, isoproterenol prodrugs; solution	Nebulization, instillation	HPLC	[162, 163]

BSA: bovine serum albumin; ELISA: enzyme-linked immunosorbent assay; HPLC: high-pressure liquid chromatography; LC-MS/MS: liquid chromatography-tandem mass spectrometry; RIA: radioimmunoassay.