RT Journal Article
T1 Insights into the mechanisms of interaction between inhalable lipid-polymer hybrid nanoparticles and pulmonary surfactant
A1 Xu, You
A1 Parra-Ortiz, Elisa
A1 Wan, Feng
A1 Cañadas Benito, Olga
A1 García Álvarez, María Begoña
A1 Thakur, Aneesh
A1 Franzyk, Henrik
A1 Pérez Gil, Jesús
A1 Malmsten, Martin
A1 Foged, Camilla
AB Pulmonary delivery of small interfering RNA (siRNA) using nanoparticle-based delivery systems is promising for local treatment of respiratory diseases. We designed dry powder inhaler formulations of siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) with aerosolization properties optimized for inhalation therapy. Interactions between LPNs and pulmonary surfactant (PS) determine the fate of inhaled LPNs, but interaction mechanisms are unknown. Here we used surface-sensitive techniques to study how physicochemical properties and pathological microenvironments influence interactions between siRNA-loaded LPNs and supported PS layers. PS was deposited on SiO2 surfaces as single bilayer or multilayers and characterized using quartz crystal microbalance with dissipation monitoring and Fourier-transform infrared spectroscopy with attenuated total reflection. Immobilization of PS as multilayers, resembling the structural PS organization in the alveolar subphase, effectively reduced the relative importance of interactions between PS and the underlying surface. However, the binding affinity between PS and LPNs was identical in the two models. The physicochemical LPN properties influenced the translocation pathways and retention time of LPNs. Membrane fluidity and electrostatic interactions were decisive for the interaction strength between LPNs and PS. Experimental conditions reflecting pathological microenvironments promoted LPN deposition. Hence, these results shed new light on design criteria for LPN transport through the air–blood barrier.
PB Elsevier 
SN 0021-9797
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/99037
UL https://hdl.handle.net/20.500.14352/99037
LA eng
NO Xu, You, et al. «Insights into the Mechanisms of Interaction between Inhalable Lipid-Polymer Hybrid Nanoparticles and Pulmonary Surfactant». Journal of Colloid and Interface Science, vol. 633, marzo de 2023, pp. 511-25. https://doi.org/10.1016/j.jcis.2022.11.059.
NO Comunidad de Madrid
NO European Commission
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO China Scholarship Council
NO Lundbeck Foundation (Denmark)
NO Novo Nordisk Foundation (Denmark)
NO Independent Research Fund (Denmark)
NO Hørslev-Fonden (Denmark)
DS Docta Complutense
RD 12 abr 2025