Abstract
Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with α2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of α2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble α2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of α2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of α2MG with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis.
| Original language | English |
|---|---|
| Pages (from-to) | 284-292 |
| Number of pages | 9 |
| Journal | Journal of Controlled Release |
| Volume | 217 |
| DOIs | |
| Publication status | Published - 10 Nov 2015 |
| Externally published | Yes |
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Keywords
- Alpha-2-macroglobulin
- Inflammation
- LbL microcapsules
- Leukocyte activation
- Phagocytosis
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response. / Canova, Donata Federici; Pavlov, Anton M.; Norling, Lucy V.; Gobbetti, Thomas; Brunelleschi, Sandra; Le Fauder, Pauline; Cenac, Nicolas; Sukhorukov, Gleb B.; Perretti, Mauro.
In: Journal of Controlled Release, Vol. 217, 10.11.2015, p. 284-292.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response
AU - Canova, Donata Federici
AU - Pavlov, Anton M.
AU - Norling, Lucy V.
AU - Gobbetti, Thomas
AU - Brunelleschi, Sandra
AU - Le Fauder, Pauline
AU - Cenac, Nicolas
AU - Sukhorukov, Gleb B.
AU - Perretti, Mauro
PY - 2015/11/10
Y1 - 2015/11/10
N2 - Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with α2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of α2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble α2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of α2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of α2MG with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis.
AB - Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with α2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of α2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble α2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of α2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of α2MG with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis.
KW - Alpha-2-macroglobulin
KW - Inflammation
KW - LbL microcapsules
KW - Leukocyte activation
KW - Phagocytosis
UR - http://www.scopus.com/inward/record.url?scp=84942885167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942885167&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2015.09.021
DO - 10.1016/j.jconrel.2015.09.021
M3 - Article
AN - SCOPUS:84942885167
VL - 217
SP - 284
EP - 292
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -