Enabling Marangoni flow at air-liquid interfaces through deposition of aerosolized lipid dispersions

Abstract

It has long been known that deposited drops of surfactant solution induce Marangoni flows at air-liquid interfaces. These surfactant drops create a surface tension gradient, which causes an outward flow at the fluid interface. We show that aqueous phospholipid dispersions may be used for this same purpose. In aqueous dispersions, phospholipids aggregate into vesicles that are not surface-active; therefore, drops of these dispersions do not initiate Marangoni flow. However, aerosolization of these dispersions disrupts the vesicles, allowing access to the surface-active monomers within. These lipid monomers do have the ability to induce Marangoni flow. We hypothesize that monomers released from broken vesicles adsorb on the surfaces of individual aerosol droplets and then create localized surface tension reduction upon droplet deposition. Deposition of lipid monomers via aerosolization produces surface tensions as low as 1 mN/m on water. In addition, aerosolized lipid deposition also drives Marangoni flow on entangled polymer solution subphases with low initial surface tensions (~ 34 mN/m.) The fact that aerosolization of phospholipids naturally found within pulmonary surfactant can drive Marangoni flows on low surface tension liquids suggests that aerosolized lipids may be used to promote uniform pulmonary drug delivery without the need for exogenous spreading agents.

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

“…(4)(5)(6)(7)(8) Recently, Marangoni stresses have been harnessed to enhance the surface transport of mock drugs deposited from surfactant-laden aerosols onto surfaces that mimic the key features of the airway surface liquid (ASL). (9)(10)(11)(12)(13)(14)(15) Researchers have been studying the use of Marangoni flows to cause surface transport for years. (16)(17)(18)(19) Marangoni flows occur when surface stresses are generated by a gradient in surface tension along an interface.…”

“…Our group has been exploring the use of phospholipids as spreading agents. (15) Because the phospholipid dipalmitoylphosphatidylcholine (DPPC) is endogenous to the lung, it is a prime candidate for addition to aerosols as an exogenous surfactant to enhance their spreading. However, its low solubility requires that it be dispersed in water in the form of vesicles before incorporation into aqueous aerosols for deposition in the lung.…”

“…While macroscopic drops of lipid dispersion do not induce Marangoni stresses after deposition on an aqueous subphase, direct deposition of aerosolized lipid dispersions does induce flow, even on low surface tension and high viscosity subphases such as porcine gastric mucin (PGM) solutions. (15) The aerosolization process breaks the lipid vesicles in the dispersion, populating the air/water interface of the aerosol with monomeric lipid molecules. This may lead to DPPC surface layers with different structures than those achieved by typical laboratory preparation methods, such as depositing drops of DPPC in a chloroform solution, which are discussed later.…”

“…The aerosolization process allows the lipid monomers to adsorb to the air/liquid interface upon deposition onto the subphase, where they then lower the surface tension and induce Marangoni flow. (15) Furthermore, the deposition of the aerosol droplets allows the surface to reach ultralow surface tensions, <5 mN/m, which are generally only obtainable under extremely slow compression of a lipid monolayer or on area cycling in a Langmuir trough. (15,20,21) Attaining these ultralow surface tensions in the deposition region means that a surface tension gradient will be generated by the aerosol deposition and flow will occur even on subphases with initially low surface tensions.…”

“…(15) Furthermore, the deposition of the aerosol droplets allows the surface to reach ultralow surface tensions, <5 mN/m, which are generally only obtainable under extremely slow compression of a lipid monolayer or on area cycling in a Langmuir trough. (15,20,21) Attaining these ultralow surface tensions in the deposition region means that a surface tension gradient will be generated by the aerosol deposition and flow will occur even on subphases with initially low surface tensions. (15) Marangoni flow is also associated with subsurface flows that provide an additional possible transport path for nonsurface-active drugs included in the aerosol formulation.…”