Biopharmaceutical Assessment of Mesh Aerosolised Plasminogen, a Step towards ARDS Treatment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Plasminogen (PLG-OMP) Aerosolisation
2.3. Maintenance of Enzymatic Activity
2.4. Protein Characterisation
2.5. Droplet Distribution of Nebulised PLG-OMP
2.6. Penetration of Aerosolised PLG through Artificial Mucus
2.7. Biological Investigation
2.7.1. PLG Permeability across an In Vitro Model of Pulmonary Epithelium
Cytotoxicity Screening on NCI-H441 Cells by Tetrazolium Salts Assay (WST-1)
In Vitro Air–Liquid Interface (ALI) Model
Assessment of Nebulised PLG Permeation through ALI Monolayer
2.7.2. Immunomodulating Activity of Nebulised PLG
2.8. Statistical Analysis
3. Results
3.1. PLG Aerosolisation under Air or Oxidising Condition
3.2. Aerosolised PLG Mobility in Simulated Mucus
3.3. PLG Permeability across a Monolayer
3.4. Maintenance of PLG Immunomodulatory Activity
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Samples | BAND% ± SD% | |||
---|---|---|---|---|
Glu-I | Glu-II | Lys-I | Lys-II | |
STD Glu PLG | 66 | 35 | - | - |
STD Lys PLG | - | - | 62 | 38 |
CTRL | 65 | 35 | - | - |
Neb PLG air | 64 ± 4.5 | 36 ± 7.9 | - | - |
Neb PLG ox | 59 ± 8.8 | 39 ± 10.3 | - | - |
Simulation of the Nebulised Protein Distribution | |
---|---|
TSI Portion | % ± SD |
Junction (T-piece) | 11.5 ± 9.7 |
Throat | 0.2 ± 0.2 |
Lower respiratory tract | 80.8 ± 5.7 |
Exhaled | 10.2 ± 9.2 |
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Vizzoni, L.; Migone, C.; Grassiri, B.; Zambito, Y.; Ferro, B.; Roncucci, P.; Mori, F.; Salvatore, A.; Ascione, E.; Crea, R.; et al. Biopharmaceutical Assessment of Mesh Aerosolised Plasminogen, a Step towards ARDS Treatment. Pharmaceutics 2023, 15, 1618. https://doi.org/10.3390/pharmaceutics15061618
Vizzoni L, Migone C, Grassiri B, Zambito Y, Ferro B, Roncucci P, Mori F, Salvatore A, Ascione E, Crea R, et al. Biopharmaceutical Assessment of Mesh Aerosolised Plasminogen, a Step towards ARDS Treatment. Pharmaceutics. 2023; 15(6):1618. https://doi.org/10.3390/pharmaceutics15061618
Chicago/Turabian StyleVizzoni, Lucia, Chiara Migone, Brunella Grassiri, Ylenia Zambito, Baldassare Ferro, Paolo Roncucci, Filippo Mori, Alfonso Salvatore, Ester Ascione, Roberto Crea, and et al. 2023. "Biopharmaceutical Assessment of Mesh Aerosolised Plasminogen, a Step towards ARDS Treatment" Pharmaceutics 15, no. 6: 1618. https://doi.org/10.3390/pharmaceutics15061618