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

Donata Federici Canova, Anton M. Pavlov, Lucy V. Norling, Thomas Gobbetti, Sandra Brunelleschi, Pauline Le Fauder, Nicolas Cenac, Gleb B. Sukhorukov, Mauro Perretti

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 languageEnglish
Pages (from-to)284-292
Number of pages9
JournalJournal of Controlled Release
Volume217
DOIs
Publication statusPublished - 10 Nov 2015
Externally publishedYes

Fingerprint

alpha-Macroglobulins
Innate Immunity
Capsules
Macroglobulins
Leukocytes
Dextrans
Sepsis
Macrophages
Drug Compounding
Exudates and Transudates
Phagocytosis
Intravenous Administration
Endothelium
Rodentia
Mass Spectrometry
Proteins
Neutrophils
Pharmacokinetics
Inflammation
Lipids

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Canova, D. F., Pavlov, A. M., Norling, L. V., Gobbetti, T., Brunelleschi, S., Le Fauder, P., ... Perretti, M. (2015). Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response. Journal of Controlled Release, 217, 284-292. https://doi.org/10.1016/j.jconrel.2015.09.021

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 journalArticle

Canova, DF, Pavlov, AM, Norling, LV, Gobbetti, T, Brunelleschi, S, Le Fauder, P, Cenac, N, Sukhorukov, GB & Perretti, M 2015, 'Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response', Journal of Controlled Release, vol. 217, pp. 284-292. https://doi.org/10.1016/j.jconrel.2015.09.021
Canova, Donata Federici ; Pavlov, Anton M. ; Norling, Lucy V. ; Gobbetti, Thomas ; Brunelleschi, Sandra ; Le Fauder, Pauline ; Cenac, Nicolas ; Sukhorukov, Gleb B. ; Perretti, Mauro. / Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response. In: Journal of Controlled Release. 2015 ; Vol. 217. pp. 284-292.
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