Aerosolizing Lipid Dispersions Enables Antibiotic Transport Across Mimics of the Lung Airway Surface Even in the Presence of Pre-existing Lipid Monolayers

Iasella, Steven V.; Stetten, Amy Z.; Corcoran, Timothy E.; Garoff, Stephen; Przybycien, Todd M.; Tilton, Robert D.

doi:10.1089/jamp.2017.1412

Cited by 11 publications

(14 citation statements)

References 36 publications

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“…Various pulmonary therapies, such as surfactant replacement therapy (SRT), depend on Marangoni spreading . There is also proposed pulmonary therapy intended to enhance postdeposition dispersal in aerosol drug delivery with surfactants. , Since endogenous pulmonary surfactant is present to differing degrees in different parts of the lung, exogenous surfactant added during treatment must induce spreading against the endogenous surfactant monolayer. The main lipid component of endogenous pulmonary surfactant is dipalmitoylphosphatidylcholine (DPPC).…”

Section: Introductionmentioning

confidence: 99%

Surfactant Driven Marangoni Spreading in the Presence of Predeposited Insoluble Surfactant Monolayers

et al. 2021

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When an insoluble surfactant is deposited on the surface of a thin fluid film, stresses induced by surface tension gradients drive Marangoni spreading across the subphase surface. The presence of a predeposited layer of an insoluble surfactant alters that spreading. In this study, the fluid film was aqueous, the predeposited insoluble surfactant was dipalmitoylphosphatidylcholine (DPPC), and the deposited insoluble surfactant was oleic acid. An optical density-based method was used to measure subphase surface distortion, called the Marangoni ridge, associated with propagation of the spreading front. The movement of the Marangoni ridge was correlated with movement of surface tracer particles that indicated both the boundary between the two surfactant layers and the surface fluid velocities. As the deposited oleic acid monolayer spread, it compressed the predeposited DPPC monolayer. During spreading, the surface tension gradient extended into the predeposited monolayer, which was compressed nonuniformly, from the deposited monolayer. The spreading was so rapid that the compressed predeposited surfactant could not have been in quasi-equilibrium states during the spreading. As the initial concentrations of the predeposited surfactant were increased, the shape of the Marangoni ridge deformed. When the initial concentration of the predeposited surfactant reached about 70 A2/molecule, there was no longer a Marangoni ridge but rather a broadly distributed excess of fluid above the initial fluid height. The nonuniform compression of the annulus of the predeposited monolayer also caused tangential motion ahead of both the Marangoni ridge and the boundary between the two monolayers. Spreading ceased when the two monolayers reached the same final surface tension. The final area per molecule of the DPPC monolayer matched that expected from the equilibrium DPPC isotherm at the same final surface tension. Thus, at the end of spreading, there was a simple surface tension balance between the two distinct monolayers.

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Section: Introductionmentioning

confidence: 99%

Surfactant Driven Marangoni Spreading in the Presence of Predeposited Insoluble Surfactant Monolayers

et al. 2021

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“…This phospholipid-induced Marangoni transport has been observed on water as well as on a 5% porcine gastric mucin (PGM) solution consisting of high-molecular weight mucins to mimic ASL (see Figure 5A) [90]. These solutions have initial surface tensions significantly lower than that of water (~ 34 mN/m), yet this does not hinder transport.…”

Section: Use Of Phospholipids and Srts For Marangoni Transport In mentioning

confidence: 80%

“…Iasella and collaborators have shown that subsurface flows induced by phospholipid Marangoni transport are sufficient to carry the antibiotic tobramycin outward from the region of aerosol deposition on mucin solution subphases with pre-deposited lipid monolayers (see Figure 6) [90]. When tobramycin was added to the aerosolized phospholipid dispersions at clinically appropriate concentrations, antibiotic concentrations of over 8 μg/mL were found across the PGM solution surface as far as 8.5 cm away from the region of deposition.…”

Section: Use Of Phospholipids and Srts For Marangoni Transport In mentioning

confidence: 99%

“…In (B) the lipid monolayer is deposited at negative times and aerosolization begins at time t = 0. Reprinted with permission from reference [90].…”

Section: Figurementioning

confidence: 99%

“…The tobramycin concentration is normalized by the total deposited dose for a given run. Reprinted with permissions from references [55] (upper panel) and [90] (lower panel).…”

Section: Figurementioning

confidence: 99%

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Surfactant-induced Marangoni transport of lipids and therapeutics within the lung

Stetten

Iasella

Corcoran

et al. 2018

Current Opinion in Colloid & Interface Science

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Understanding the fundamentals of surface transport on thin viscous films has important application in pulmonary drug delivery. The human lung contains a large-area interface between its complex fluid lining and inhaled air. Marangoni flows driven by surface tension gradients along this interface would promote enhanced distribution of inhaled therapeutics by carrying them from where they are deposited in the upper airways, along the fluid interface to deeper regions of the lung. Motivated by the potential to improve therapies for acute and chronic lung diseases, we review recent progress in modeling and experimental studies of Marangoni transport induced by the deposition of surfactant-containing microliter drops and liquid aerosols (picoliter drops) onto a fluid interface. The roles of key system variables are identified, including surfactant solubility, drop miscibility with the subphase, and the thickness, composition and surface properties of the subphase liquid. Of particular interest is the unanticipated but crucial role of aerosol processing to achieve Marangoni transport via phospholipid vesicle dispersions, which are likely candidates for a biocompatible delivery system. Progress in this field has the potential to not only improve outcomes in patients with chronic and acute lung diseases, but also to further our understanding of surface transport in complex systems.

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Surfactant-mediated wetting and spreading: Recent advances and applications

Kovalchuk

Simmons

2021

Current Opinion in Colloid & Interface Science

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Aerosolizing Lipid Dispersions Enables Antibiotic Transport Across Mimics of the Lung Airway Surface Even in the Presence of Pre-existing Lipid Monolayers

Cited by 11 publications

References 36 publications

Surfactant Driven Marangoni Spreading in the Presence of Predeposited Insoluble Surfactant Monolayers

Surfactant Driven Marangoni Spreading in the Presence of Predeposited Insoluble Surfactant Monolayers

Surfactant-induced Marangoni transport of lipids and therapeutics within the lung

Surfactant-mediated wetting and spreading: Recent advances and applications

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