TY - JOUR

T1 - Effect of lipid-polymer hybrid nanoparticles on the biophysical function and lateral structure of pulmonary surfactant

T2 - Mechanistic in vitro studies

AU - Xu, You

AU - Cañadas, Olga

AU - Alonso, Alejandro

AU - Franzyk, Henrik

AU - Thakur, Aneesh

AU - Pérez-gil, Jesús

AU - Foged, Camilla

N1 - Funding Information: We gratefully acknowledge the financial support from the Novo Nordisk Foundation, Denmark (grant no. NNF17OC0026526), Independent Research Fund, Denmark (grant no. DFF-4184-00422), the regional Government of Madrid (grant no. P2018/NMT4389), and the Spanish Ministry of Science and Innovation (grant no. PID2021-124932OB-I00). We acknowledge the China Scholarship Council (CSC) for the Scholarship to You Xu (grant no. 201906210064). Funding Information: We thank Abhijeet Girish Lokras and Akash Chakravarty for purifying L5N12. We thank Paula Losada for helping with the graphical abstract. Publisher Copyright: © 2023 Elsevier Inc.

PY - 2024

Y1 - 2024

N2 - The interaction between inhaled drug-loaded nanoparticles and pulmonary surfactant (PS) is critical for the efficacy and safety of inhaled nanomedicines. Here, we investigated the effect of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs), which are designed for treatment of lung inflammation, on the physiological function of PS. By using biophysical in vitro methods we show that siRNA-loaded LPNs affect the biophysical function and lateral structure of PS. We used the Langmuir monolayer technique to demonstrate that LPNs display intrinsic surface activity by forming interfacial films that collapse at 49 mN/m, and they competitively inhibit the adsorption and spreading of PS components at the air–liquid interface. However, LPNs are excluded from the interface into the aqueous subphase at surface pressures above 49 mN/m, and hence they overcome the PS monolayer film barrier. Epifluorescence microscopy data revealed that LPNs influence the lateral structure of PS by: (i) affecting the nucleation, shape, and growth of compression-driven segregated condensed PS domains, and (ii) facilitating intermixing of liquid-expanded and tilted-condensed domains. However, the total surface area occupied by a highly condensed phase, presumably enriched in the highly surface tension-reducing dipalmitoylphosphatidylcholine, remained constant upon exposure to LPNs. These results suggest that surface-active LPNs influence the lateral structure of PS during translocation from the interface into the subphase, but LPNs do apparently not affect the biophysical function of PS under physiologically relevant conditions.

AB - The interaction between inhaled drug-loaded nanoparticles and pulmonary surfactant (PS) is critical for the efficacy and safety of inhaled nanomedicines. Here, we investigated the effect of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs), which are designed for treatment of lung inflammation, on the physiological function of PS. By using biophysical in vitro methods we show that siRNA-loaded LPNs affect the biophysical function and lateral structure of PS. We used the Langmuir monolayer technique to demonstrate that LPNs display intrinsic surface activity by forming interfacial films that collapse at 49 mN/m, and they competitively inhibit the adsorption and spreading of PS components at the air–liquid interface. However, LPNs are excluded from the interface into the aqueous subphase at surface pressures above 49 mN/m, and hence they overcome the PS monolayer film barrier. Epifluorescence microscopy data revealed that LPNs influence the lateral structure of PS by: (i) affecting the nucleation, shape, and growth of compression-driven segregated condensed PS domains, and (ii) facilitating intermixing of liquid-expanded and tilted-condensed domains. However, the total surface area occupied by a highly condensed phase, presumably enriched in the highly surface tension-reducing dipalmitoylphosphatidylcholine, remained constant upon exposure to LPNs. These results suggest that surface-active LPNs influence the lateral structure of PS during translocation from the interface into the subphase, but LPNs do apparently not affect the biophysical function of PS under physiologically relevant conditions.

KW - Air–liquid interface

KW - Biophysical function

KW - Interfacial adsorption

KW - Lateral structure

KW - Nanoparticle translocation

KW - Pulmonary drug delivery

KW - Surface activity

U2 - 10.1016/j.jcis.2023.10.036

DO - 10.1016/j.jcis.2023.10.036

M3 - Journal article

VL - 654

SP - 1111

EP - 1123

JO - Journal of Colloid and Interface Science

JF - Journal of Colloid and Interface Science

SN - 0021-9797

IS - Part B

ER -