科研之友
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摘要
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 (alpha 2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with alpha 2MG 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 alpha 2MG 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 alpha 2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of alpha 2MG-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 alpha 2MGZ with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis.
- 出版日期2015-11-10
