TY - JOUR

T1 - Dynamics of Phosphatidylcholines in the Bronchoalveolar Lavage of Mice After the Introduction of Essential Phospholipids

AU - Yurin, V V

AU - An'kov, S V

AU - Bogatishcheva, K S

AU - Sotnikova, M A

AU - Basov, N V

AU - Rogachev, A D

AU - Osechkova, A E

AU - Sotnikova, Yu S

AU - Patrushev, Y V

AU - Prokopyeva, E A

AU - Dolgova, N A

AU - Tolstikova, T G

AU - Dultseva, G G

AU - Grishin, O V

AU - Valiulin, S V

AU - Salakhutdinov, N F

AU - Pokrovsky, A G

N1 - All experiments involving laboratory animals were carried out with financial support from Ministry of Science and Higher Education of theRussian Federation within the State Assignment for NIOCh SB RAS no. 075-00365-25-00. The monolith columns were manufactured with support withinthe project no. FWUR-2024-0032. Sample preparation and analysis by HPLC-MS/MS were supported within the state assignment no. FSUS-2020-0035. Inhalation experiments were carried out at ICKC SB RAS within the state assignment no. FWGF-2021-0004.

PY - 2025/12

Y1 - 2025/12

N2 - Lung surfactant is a lipid-protein complex essential for maintaining alveolar stability by reducing surface tension. In surfactant-deficient states such as pneumonia or acute respiratory distress syndrome, alveolar collapse and impaired gas exchange may occur. Exogenous supplementation of surfactant phospholipids has been proposed to improve lung function. In this work, we performed LC-MS/MS analysis of phosphatidylcholines from a commercially available Essentiale phospholipid preparation in bronchoalveolar lavage (BAL) fluid. The dynamics of BAL phosphatidylcholine levels in mice following intravenous and aerosol administration of Essentiale were investigated for the first time, revealing the time course and extent of pulmonary accumulation for each route. A 20-min aerosol inhalation of Essentiale (≈3 mg/kg phospholipids) achieved BAL phosphatidylcholine concentrations comparable to those obtained with a 500 mg/kg intravenous dose. Repeated daily intravenous dosing caused a gradual increase in BAL phosphatidylcholine over 3-4 days, whereas prolonged aerosol exposure beyond 20 min did not further elevate BAL levels, likely due to uptake by alveolar cells. These findings highlight aerosol inhalation as a more efficient delivery method for surfactant phospholipids and suggest an optimal dosing regimen (≈ 3 mg/kg, 20 min) for adjunctive therapy in conditions associated with surfactant deficiency.

AB - Lung surfactant is a lipid-protein complex essential for maintaining alveolar stability by reducing surface tension. In surfactant-deficient states such as pneumonia or acute respiratory distress syndrome, alveolar collapse and impaired gas exchange may occur. Exogenous supplementation of surfactant phospholipids has been proposed to improve lung function. In this work, we performed LC-MS/MS analysis of phosphatidylcholines from a commercially available Essentiale phospholipid preparation in bronchoalveolar lavage (BAL) fluid. The dynamics of BAL phosphatidylcholine levels in mice following intravenous and aerosol administration of Essentiale were investigated for the first time, revealing the time course and extent of pulmonary accumulation for each route. A 20-min aerosol inhalation of Essentiale (≈3 mg/kg phospholipids) achieved BAL phosphatidylcholine concentrations comparable to those obtained with a 500 mg/kg intravenous dose. Repeated daily intravenous dosing caused a gradual increase in BAL phosphatidylcholine over 3-4 days, whereas prolonged aerosol exposure beyond 20 min did not further elevate BAL levels, likely due to uptake by alveolar cells. These findings highlight aerosol inhalation as a more efficient delivery method for surfactant phospholipids and suggest an optimal dosing regimen (≈ 3 mg/kg, 20 min) for adjunctive therapy in conditions associated with surfactant deficiency.

KW - Animals

KW - Phosphatidylcholines/analysis

KW - Bronchoalveolar Lavage Fluid/chemistry

KW - Mice

KW - Tandem Mass Spectrometry/methods

KW - Phospholipids/administration & dosage

KW - Male

KW - Chromatography, Liquid/methods

KW - Administration, Inhalation

U2 - 10.1002/bmc.70259

DO - 10.1002/bmc.70259

M3 - Article

C2 - 41218812

VL - 39

JO - Biomedical chromatography

JF - Biomedical chromatography

SN - 0269-3879

IS - 12

M1 - e70259

ER -