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J Control Release. 2015 Nov 10;217:284-92. doi: 10.1016/j.jconrel.2015.09.021. Epub 2015 Sep 16.

Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response.

Author information

1
William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
2
School of Engineering & Materials Science, Queen Mary University of London, London, United Kingdom; Saratov State University, Saratov, Russia.
3
Department of Health Science, University of Eastern Piedmont, Novara, Italy.
4
MetaToul Lipidomics Facility, INSERM UMR1048, Toulouse, France.
5
INSERM UMR1043, Université Toulouse III Paul-Sabatier, Toulouse, France.
6
School of Engineering & Materials Science, Queen Mary University of London, London, United Kingdom.
7
William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom. Electronic address: m.perretti@qmul.ac.uk.

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.

KEYWORDS:

Alpha-2-macroglobulin; Inflammation; LbL microcapsules; Leukocyte activation; Phagocytosis

PMID:
26385167
PMCID:
PMC4649706
DOI:
10.1016/j.jconrel.2015.09.021
[Indexed for MEDLINE]
Free PMC Article

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