Ultrasonic and Jet Aerosolization of Phospholipids and the Effects on Surface Activity

Abstract

Summarytive dose theraw might be beneficial in the treatment of RDS, Surface active aerosols were produced from aqueous dispersions of mixed lipids (CLL), extracted fnnn bovine lung lavage. Particle size distributioas were measured as a funetion of humMity far two types of aerosol generators: ultrrrsoaif and jet. Lipid dispersions betore aerosolhation were prepared by sonication in an ice bath and by mechanical vortexing. Over a range of bigh huaddity greater than 60-70%, ultrasonic nebulization gave CLL lerosds with mass median aerodynamic diameters (MMAD) of 1.4 * 0.1 pm, compatible with predicted alveolar deposition fractions of 03-0.3 according to current deposition models. For humidities of 30-%%, jet nebulization gave MMAD values of 0.4-03 pm, rrhicb have lower predicted alveolar deposition. The surface pressuretime (n -t) adsomtion characteristics at 35 * 2OC of CLL dispe&ions &epari initially by vortexing or sonication were not significantly affected by ultrasonic nebulization over a 1-2 h time period. In addition, the dynamic surface tension lowering of both W s of CLL dispersion was not affected by ultrasonic nebulizrrtioo (minimum surface tension <I dyne/cm at 37OC and 100% humidity). Current interest in the treatment of the respiratory distress syndrome (RDS) with exogenous surfactant replacement has focused largely on the delivery of surfactants to infants by tracheal instiUation at b i d . However, the ability to form multicomponent surfactant aerosols with appreciable alveolar deposition fractions Pad bigh surface activity may help to expand the utility of replacement therapy to patients with aerated luogs. Abbreviations CLL, calf lung lipids DPPC, dipalmitoyl phosphatidylcholine DPPC, dipalmitoyl phosphatidylglycerol egg-PC, egg phosphatidylglycerol LPC, lyso-phosphatidylcholine MMAD, mass median aerodynamic diameter n, surface pressure n -t, surface pressure-time PC, phosphatidylcboline RDS, respiratory distress syndrome Sl, sonication in an ice bath.TLC, thin layer chromatography V, mechanical vortexing at room temperature Much of the present interest in exogenous surfactant replacement therapy for neonatal RDS is centered on the delivery of surfactant mixtures to the respiratory system by direct airway instillation (18,22,23). In animal model experiments for such therapy, the most effective time for surfactant instillation has been found to be before, or at least very close to, the onset of breathing (22). Current research (e.g., 10) also indicates that a single preventilatory dose of exogenous surfactant material can have an initial beneficial effect on lung function, which then decreases with time after instillation. The possibility thus exists that repetiand this in turn'iaises-the question of what method might be most appropriate for the delivery of surfactants to aerated lungs.Although tracheal instillation may be a preferred method for lungs in the initial stage of ventilation, a useful technique for surfactant delivery to aerated alveoli is by surface active aerosols. Studies by several...

Lung Deposition of Nebulized Surfactant in Newborn Piglets

“…This is about the same as the endogenous pool size of surfactant in newborn immature lambs that breathed well enough to avoid hypercapnia [23]. In a study by Marks et al [24], the amount of surfactant needed to cover the alveolar surface with a close-packed monolayer was calculated to be 3.1 mg·kg -1 . However, there is no evidence that such small amounts can have a clinical effect when delivered by inhalation.…”

Surfactant for Pediatric Acute Lung Injury

“…Typical doses of intratracheal surfactant in premature infants are 100 mg/kg body weight. This represents a significant excess over the amount of surfactant phospholipid needed to cover the surface of the alveolar network with a tightly packed surfactant film (only about 3 mg/kg of surfactant phospholipid at a molecular weight of 750 Daltons are needed to form a monomolecular film at a limiting area of 40 Å 2 /molecule over an alveolar surface of 1 m 2 /kg body weight [46,150]). Excess instilled exogenous surfactant that reaches the alveoli provides a reservoir of material for the hypophase and interface, and is available for incorporation into endogenous surfactant pools via recycling pathways.…”

“…In theory, aerosolization could significantly reduce required surfactant doses, since delivery can be targeted to the alveoli by controlling particle size. Phospholipid aerosols with stable particle sizes appropriate for alveolar deposition in normal lungs can be formed by ultrasonic or jet nebulization [150,156,157], and exogenous surfactants have been aerosolized to animals and patients with surfactant deficiency or dysfunction [91,105,110,136,[158][159][160]. However, the theoretical potential of aerosols to improve alveolar deposition and reduce required surfactant doses has not been replicated in practice.…”

The Future of Exogenous Surfactant Therapy

“…157,158,173 Aero-sol delivery to the alveoli in normal lungs is maximal in the particle-size range 0.5-2.0 m, and it is possible to generate a stable surfactant aerosol with that particle size range from aqueous or powdered surfactant. 135,174,175 A recent study by Ruppert et al 135 demonstrated the ability to deliver substantial amounts of a powder recombinant protein C surfactant aerosol with a new aerosol generator to improve oxygenation and compliance in lung-lavaged rabbits. However, whether surfactant aerosolization can be accomplished in a sufficiently effective and efficient manner to replace instillation requires further and more detailed direct comparisons in animals and subsequently in human trials.…”