2026-08-24T05:19:06Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/990372024-08-19T23:48:03Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Xu, You author Parra-Ortiz, Elisa author Wan, Feng author Cañadas Benito, Olga author García Álvarez, María Begoña author Thakur, Aneesh author Franzyk, Henrik author Pérez Gil, Jesús author Malmsten, Martin author Foged, Camilla author 2022 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. 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. 0021-9797 10.1016/j.jcis.2022.11.059 https://hdl.handle.net/20.500.14352/99037 https://doi.org/10.1016/j.jcis.2022.11.059 Insights into the mechanisms of interaction between inhalable lipid-polymer hybrid nanoparticles and pulmonary surfactant