Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge
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 ni...
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | http://link.springer.com/article/10.1186/s12951-018-0364-z |
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| author | Fu-Chao Liu Huang-Ping Yu Cheng-Yu Lin Ahmed O. Elzoghby Tsong-Long Hwang Jia-You Fang |
| author_facet | Fu-Chao Liu Huang-Ping Yu Cheng-Yu Lin Ahmed O. Elzoghby Tsong-Long Hwang Jia-You Fang |
| author_sort | Fu-Chao Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T06:14:38Z |
| format | Article |
| id | doaj.art-8f20de41df2b4df78620f32caece9311 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T06:14:38Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-8f20de41df2b4df78620f32caece93112022-12-22T02:58:54ZengBMCJournal of Nanobiotechnology1477-31552018-03-0116111410.1186/s12951-018-0364-zUse of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface chargeFu-Chao Liu0Huang-Ping Yu1Cheng-Yu Lin2Ahmed O. Elzoghby3Tsong-Long Hwang4Jia-You Fang5Department of Anesthesiology, Chang Gung Memorial HospitalDepartment of Anesthesiology, Chang Gung Memorial HospitalPharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung UniversityCancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria UniversityDepartment of Anesthesiology, Chang Gung Memorial HospitalDepartment of Anesthesiology, Chang Gung Memorial HospitalAbstract 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.http://link.springer.com/article/10.1186/s12951-018-0364-zCilomilastPhosphatiosomesNanovesicleAcute lung injurySurface charge |
| spellingShingle | Fu-Chao Liu Huang-Ping Yu Cheng-Yu Lin Ahmed O. Elzoghby Tsong-Long Hwang Jia-You Fang Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge Journal of Nanobiotechnology Cilomilast Phosphatiosomes Nanovesicle Acute lung injury Surface charge |
| title | Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge |
| title_full | Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge |
| title_fullStr | Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge |
| title_full_unstemmed | Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge |
| title_short | Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge |
| title_sort | use of cilomilast loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury the effect of nanovesicular surface charge |
| topic | Cilomilast Phosphatiosomes Nanovesicle Acute lung injury Surface charge |
| url | http://link.springer.com/article/10.1186/s12951-018-0364-z |
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