Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: The effect of nanovesicular surface charge

Fu Chao Liu, Huang Ping Yu, Cheng Yu Lin, Ahmed O. Elzoghby, Tsong Long Hwang*, Jia You Fang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

28 Scopus citations

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.

Original languageEnglish
Article number35
JournalJournal of Nanobiotechnology
Volume16
Issue number1
DOIs
StatePublished - 30 03 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

Keywords

  • Acute lung injury
  • Cilomilast
  • Nanovesicle
  • Phosphatiosomes
  • Surface charge

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