Qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant by using quartz crystal microbalance with dissipation monitoring

Feng Wan; Tommy Nylander; Camilla Foged; Mingshi Yang; Stefania G Baldursdottir; Hanne M Nielsen

doi:10.1016/j.jcis.2019.02.088

Qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant by using quartz crystal microbalance with dissipation monitoring

J Colloid Interface Sci. 2019 Jun 1:545:162-171. doi: 10.1016/j.jcis.2019.02.088. Epub 2019 Mar 1.

Authors

Feng Wan¹, Tommy Nylander², Camilla Foged¹, Mingshi Yang¹, Stefania G Baldursdottir¹, Hanne M Nielsen³

Affiliations

¹ Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
² Department of Physical Chemistry, Lund University, SE-221 00 Lund, Sweden.
³ Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark. Electronic address: hanne.morck@sund.ku.dk.

PMID: 30877998
DOI: 10.1016/j.jcis.2019.02.088

Abstract

Understanding the interaction between inhaled nanoparticles and pulmonary surfactant is a prerequisite for predicting the fate of inhaled nanoparticles. Here, we introduce a quartz crystal microbalance with dissipation monitoring (QCM-D)-based methodology to reveal the extent and nature of the biophysical interactions of polymer- and lipid-based nanoparticles with pulmonary surfactant. By fitting the QCM-D data to the Langmuir adsorption equation, we determined the kinetics and equilibrium parameters [i.e., maximal adsorption (Δm_max), equilibrium constant (K_a), adsorption rate constant (k_a) and desorption rate constant (k_d)] of polymeric nanoparticles adsorption onto the pulmonary surfactant (e.g., an artificial lipid mixture and an extract of porcine lung surfactant). Furthermore, our results revealed that the nature of the interactions between lipid-based nanoparticles (e.g., liposomes) and pulmonary surfactant was governed by the liposomal composition, i.e., incorporation of cholesterol and PEGylated phospholipid (DSPE-PEG₂₀₀₀) into DOPC-based liposomes led to the adsorption of intact liposomes onto the pulmonary surfactant layer and the mass exchange between the liposomes and pulmonary surfactant layer, respectively. In conclusion, we demonstrate the applicability of the QCM-D technique for qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant, which is vital for rational design and optimization of inhalable nanomedicines.

Keywords: Bio-nano interaction; Fusogenic liposomes; Inhaled nanoparticles; PLGA nanoparticles; Pulmonary surfactant; Quartz crystal microbalance with dissipation monitoring (QCM-D).