Back to Search
Start Over
Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge
- Source :
- Journal of Nanobiotechnology, Vol 16, Iss 1, Pp 1-14 (2018), Journal of Nanobiotechnology
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- Background Cilomilast is a phosphodiesterase 4 (PDE4) inhibitor for treating inflammatory lung diseases. This agent has a narrow therapeutic index with significant adverse effects on the nervous system. This study was conducted to entrap cilomilast into PEGylated phosphatidylcholine-rich niosomes (phosphatiosomes) to improve pulmonary delivery via the strong affinity to pulmonary surfactant film. Neutrophils were used as a cell model to test the anti-inflammatory activity of phosphatiosomes. In an in vivo approach, mice were given lipopolysaccharide to produce acute lung injury. The surface charge in phosphatiosomes that influenced the anti-inflammatory potency is discussed in this study. Results The average diameter of the phosphatiosomes was about 100 nm. The zeta potential of anionic and cationic nanovesicles was − 35 and 32 mV, respectively. Cilomilast in both its free and nanocapsulated forms inhibited superoxide anion production but not elastase release in activated neutrophils. Cationic phosphatiosomes mitigated calcium mobilization far more effectively than the free drug. In vivo biodistribution evaluated by organ imaging demonstrated a 2-fold ameliorated lung uptake after dye encapsulation into the phosphatiosomes. The lung/brain distribution ratio increased from 3 to 11 after nanocarrier loading. The intravenous nanocarriers deactivated the neutrophils in ALI, resulting in the elimination of hemorrhage and alveolar wall damage. Only cationic phosphatiosomes could significantly suppress IL-1β and TNF-α in the inflamed lung tissue. Conclusions These results suggest that phosphatiosomes should further be investigated as a potential nanocarrier for the treatment of pulmonary inflammation.
- Subjects :
- 0301 basic medicine
Lipopolysaccharides
Male
Cyclohexanecarboxylic Acids
Neutrophils
Anti-Inflammatory Agents
Pharmaceutical Science
Medicine (miscellaneous)
02 engineering and technology
Pharmacology
Applied Microbiology and Biotechnology
Neutrophil Activation
Cilomilast
Acute lung injury
Tissue Distribution
Lung
Chemistry
Elastase
021001 nanoscience & nanotechnology
medicine.anatomical_structure
lcsh:R855-855.5
Phosphatidylcholines
Molecular Medicine
Nanovesicle
0210 nano-technology
medicine.drug
lcsh:Medical technology
lcsh:Biotechnology
Static Electricity
Biomedical Engineering
Bioengineering
Lung injury
03 medical and health sciences
Therapeutic index
In vivo
lcsh:TP248.13-248.65
Nitriles
medicine
Animals
Humans
Niosome
Phosphatiosomes
Particle Size
Research
Surface charge
Mice, Inbred C57BL
030104 developmental biology
Liposomes
Nanoparticles
Calcium
Nanocarriers
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 14773155
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Nanobiotechnology
- Accession number :
- edsair.doi.dedup.....2976400c31e5fdb4823bc2645e2eabc5
- Full Text :
- https://doi.org/10.1186/s12951-018-0364-z