Size Dependent Interactions of Nanoparticles with Lung Surfactant Model Systems and the Significant Impact on Surface Potential

Abstract

The relationship between a model pulmonary surfactant system and various sized nanoparticles was investigated in this study. Diplamitoylphosphatidylcholine (DPPC) is the main lipid constituent of lung surfactant and has the ability to reach very high surface pressures (around 70 mN/m) upon compression. Due to these properties it was used as a model to simulate the lung surfactant film in vitro. The first objective of this study was to investigate the relationship between DPPC and various sized nanoparticles within the subphase through surface pressure-area isotherms. The second objective was to measure the surface potential of the different preparations (conducted on a mini-Langmuir trough) and to determine if an optimal nanoparticle size exists possessing a greater affinity for the DPPC film compared to other sizes. The results from the pressure area isotherms indicate that the interaction between DPPC and the nanoparticles is stable and that the 235 nm particles may represent an optimal size. Furthermore, the results from the surface potential experiments confirm that an interaction of the nanoparticles with the monolayer exists as indicated by surface-pressure area isotherms. Any even moderate interaction between nanoparticles and lung surfactant film might reduce or increase the surface potential of the surfactant film, and this might impact the deposition of the nanoparticles or other ligands which may be positively or negatively charged drugs within the surfactant film. Thus changes in surface potential due to nanoparticle interactions have to be taken into account for future drug targeting studies using nano-sized drug carriers.

Pulmonary Toxicity of Polysorbate-80-coated Inhalable Nanoparticles; In vitro and In vivo Evaluation

“…Monolayer systems as an in vitro lung surfactant model have been previously used to investigate the biophysical interaction of nano-materials with lung surfactants especially for inorganic NPs and nano-crystals (10). In the present study, we investigated the effect of polysorbate 80 as NP coating material on the integrity of the lung surfactant layer using an in vitro model.…”

“…In the lungs, the surfactant layer exists at the gaseous-surfactant interface with an aqueous subphase (10). Therefore, in order to simulate this situation, this study was designed to have NPs suspended in the aqueous subphase of the trough with DPPC monolayer film spread on top at the air-water interface.…”

“…In the alveolar space, a thin film of lung surfactant covers the epithelium. It is composed of phospholipids and proteins (10). The main component of the film is 1,2-Dipalmitoyl-snGlycero-3-Phosphocholine (DPPC), a phosphatidylcholine with two saturated 16-carbon long fatty acyl chains (11).…”

“…Changes in the surface pressure-area isotherms induced by NPs were recorded and considered as an indicator for interactions of NPs and components of the surfactant model. Previous studies investigated the effect of non-coated NPs on the integrity of the lung surfactant film in vitro (10,11,14). Azarmi et al showed in vivo that non-coated NPs are well tolerated by Balb/c nude mice after pulmonary administration (15).…”

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

“…Recent model studies revealed how charged drugs interact with the lung monolayer; NP-lung monolayer interaction can affect monolayer potential, although the structural integrity of the monolayer is well preserved. This highlights the importance of designing materials to give desired interactions between drug and cell and other biological molecules and the cell, as well as drug-NP and NP-cell interactions [140].…”