Table 9.
Comparison studies of surfactant delivery by nebulization and instillation in animal models.
| Surfactant | Dose delivered | Delivery method | Aerosol particle size | Amount deposited | Disease (model) | Notes | Ref. |
|---|---|---|---|---|---|---|---|
| [3H] NS [3H] Survanta® |
308 mg NS 248 mg Survanta |
Actuated nebulizer + MV | MMAD = 1.8–2.3 μm, GSD = ±2.1 | 5.4 mg NS 6.7 mg Survanta |
NRDS (lamb fetuses) | Compare between surfactant delivery methods and between surfactant types More surfactant deposition in the right upper lobes and tracheae in the nebulized none compared with the instilled group Aerosolized surfactant improved lung function at a very low surfactant dose |
[92] |
| [3H] NS [3H] Survanta |
50 mg NS/kg | ETT + MV before and after delivery | N/A | 96.7% NS | NRDS (lamb fetuses) | Compare between surfactant delivery methods and between surfactant types More surfactant deposition in the right upper lobes and tracheae in the nebulized none compared with the instilled group Aerosolized surfactant improved lung function at a very low surfactant dose |
[92] |
| [3H] Survanta |
20 mg PL/ml (12.3 ml) | A low-flow nebulizer | MMAD = 1.6 μm, GSD = 2 | 9.1 ± 1.7 mg PL (3.6% of 12.3 ml) | Severe lung injury (rabbit) | Surfactant aerosol resulted in modest physiological improvements in lung injury model and was superior to the tracheal instillation technique | [40] |
| [3H] Survanta |
20 mg PL/ml (5 ml/kg) | ETT + MV | N/A | N/A | Severe lung injury (rabbit) | Surfactant aerosol resulted in modest physiological improvements in lung injury model and was superior to the tracheal instillation technique | [40] |
| [3H] Survanta |
528 ± 61 mg (21.1 ml) | A low-flow nebulizer | MMAD = 2–3 μm, GSD = 1.9-2.1 | 168 ± 27 mg | Non-uniform pattern of lung injury (adult sheep) | Various delivery techniques led to significant difference in distribution patterns Surfactant aerosol was poorly deposited in the severely injured regions, reflecting poor ventilation of these regions Surfactant aerosol had greater improvements in oxygenation and ventilator parameters compared with tracheal instilled animals |
[49] |
| [3H] Survanta |
4000 ± 132 mg (160 ml) | ETT | N/A | 2525 ± 251 mg | Non-uniform pattern of lung injury (adult sheep) | Various delivery techniques led to significant difference in distribution patterns Surfactant aerosol was poorly deposited in the severely injured regions, reflecting poor ventilation of these regions Surfactant aerosol had greater improvements in oxygenation and ventilator parameters compared with tracheal instilled animals |
[49] |
| [3H] Survanta |
304 ± 50 mg (12 ml) | Actuated nebulizer | MMAD = 2.2–2.8 μm, GSD = 1.9–2.1 | 6.1 ± 2.2% in the peripheral lung tissue | ALI (adult sheep) | Improved lung function with notably different amount of surfactant deposited in lung tissue for the two delivery methods Instillation was superior to aerosolization Superior distribution pattern within the lungs of aerosolized surfactant compared with instilled surfactant |
[50] |
| [3H] Survanta |
3410 ± 130 mg | ETT | N/A | 51% | ALI (adult sheep) | Improved lung function with notably different amount of surfactant deposited in lung tissue for the two delivery methods Instillation was superior to aerosolization Superior distribution pattern within the lungs of aerosolized surfactant compared with instilled surfactant |
[50] |
| [125I] Sheep NS | 25 mg PL/ml | Ultrasonic nebulized (Neb) | MAD = ~3 μm | 23.4 ± 2.5% | Lamb fetuses | The potential for nebulized surfactant therapy in RDS may be limited by the non-homogeneous nature of ventilation in the preterm lung | [94] |
| [125I] Sheep NS | 25 mg PL/ml | Inst/Inst† | N/A | 75 ± 1% | Lamb fetuses | The potential for nebulized surfactant therapy in RDS may be limited by the non-homogeneous nature of ventilation in the preterm lung | [94] |
| [125I] Sheep NS | 25 mg PL/ml | Inst/Neb‡ | N/A | 23.4 ± 2.5% | Lamb fetuses | The potential for nebulized surfactant therapy in RDS may be limited by the non-homogeneous nature of ventilation in the preterm lung | [94] |
| [99mTc] Alveofact® |
100 mg/kg | MiniNEB nebulizer | MMAD = 3 μm and 70% of particles = 1–5 μm. | N/A | RDS (rabbit) | Instillation was followed by a rapid decrease in MABP and a more marked drop in cerebral blood flow, while during nebulization, MABP did not alter and cerebral blood flow decreased less and more gradually | [109] |
| [99mTc] Alveofact |
100 mg/kg | ETT | N/A | N/A | RDS (rabbit) | Instillation was followed by a rapid decrease in MABP and a more marked drop in cerebral blood flow, while during nebulization, MABP did not alter and cerebral blood flow decreased less and more gradually | [109] |
| Alveofact | 8.83 ± 0.69 ml of 10 mg/ml | Ultrasonic nebulized | MMAD = 4.5 μm GSD = 2.6 |
20.4 ± 1.5 mg | ALI (isolated rabbit lungs) | Nebulizers used for efficient delivery of surfactant to the distal bronchoalveolar space Low amounts of inhaled surfactant may be more effective in improving gas exchange than large amounts of instilled substance |
[27] |
| Alveofact | 30 mg | ETT | N/A | 30.0 ± 0.0 mg | ALI (isolated rabbit lungs) | Nebulizers used for efficient delivery of surfactant to the distal bronchoalveolar space Low amounts of inhaled surfactant may be more effective in improving gas exchange than large amounts of instilled substance |
[27] |
| [99mTc] Alveofact |
100 mg/kg (1.8 ± 0.1 kg) | Miniheart low-flow nebulizer + HFV | MMAD = 3 μm and 70% of particles = 1–5 μm. | 9.8% | RDS (rabbit) | Aerosols during HFV improved lung function at low alveolar dose without improving distribution, with less effect on blood pressure and cerebral blood flow compared with surfactant instillation Both modes of surfactant treatment led to non-uniform distribution with less uniform distribution after nebulization |
[2] |
| [99mTc] Alveofact |
100 mg/kg (1.8 ± 0.1 kg) | Instillation as a bolus injection + HFV | N/A | 91% | RDS (rabbit) | Aerosols during HFV improved lung function at low alveolar dose without improving distribution, with less effect on blood pressure and cerebral blood flow compared with surfactant instillation Both modes of surfactant treatment led to non-uniform distribution with less uniform distribution after nebulization |
[2] |
| Alveofact | 36.4 mg/kg | Ultrasonic nebulized | MMAD = 4.5 μm and GSD = 2.3 | 8.6 mg/kg | ALI (rabbit lungs: 2.5–3.1 kg) | Low doses of aerosols are similarly effective as normal doses of instilled surfactant in reducing shunt flow in ALI model, but apply more beneficial effects on ventilation perfusion matching | [101] |
| Alveofact | 80 mg/kg | ETT | N/A | N/A | ALI (rabbit lungs: 2.5–3.1 kg) | Low doses of aerosols are similarly effective as normal doses of instilled surfactant in reducing shunt flow in ALI model, but apply more beneficial effects on ventilation perfusion matching | [101] |
| Porcine surfactant | 800 mg/kg | Nebulizer | ≥2.0 μm | 25 mg/kg | OA induce ALI (rat: 0.2–0.25 kg) | Aerosolized surfactant inhaled by spontaneous breathing may effectively reduce severe lung injury It is simple, safe and combines the therapeutic effects of a surfactant with partial oxygen inhalation under spontaneous breathing |
[12] |
| Porcine surfactant | 100 mg/kg | ETT | N/A | N/A | OA induce ALI (rat: 0.2–0.25 kg) | Aerosolized surfactant inhaled by spontaneous breathing may effectively reduce severe lung injury. It is simple, safe and combines the therapeutic effects of a surfactant with partial oxygen inhalation under spontaneous breathing |
[12] |
†
Inst/Inst: Animals received instilled surfactant followed by a second instilled dose.
‡
Inst/Neb: Animals received instilled surfactant followed by a nebulized surfactant.
ALI: Acute lung injury; ETT: Endotracheal tube; GSD: Geometric standard deviation; HFV: High frequency ventilator; MABP: Mean arterial blood pressure; MMAD: Mass median aerodynamic diameter; MV: Mechanical ventilation: Neb: Nebulized surfactant; NS: Natural surfactant; NRDS: Neonates with respiratory distress syndrome; OA: Oleic acid; PL: Phospholipids; RDS: Respiratory distress syndrome.