Macrophage depletion induced by clodronate-loaded erythrocytes

Luigia Rossi, Sonja Serafini, Antonella Antonelli, Francesca Pierigé, Andrea Carnevali, Valeria Battistelli, Manuela Malatesta, Emanuela Balestra, Raffaele Caliò, Carlo Federico Perno, Mauro Magnani

Research output: Contribution to journalArticlepeer-review

Abstract

Given the important role of macrophages in various disorders, the transient and organ specific suppression of their functions may benefit some patients. Until now, liposome-encapsulated bisphosphonate clodronate has been extensively proposed to this end. In this paper, we demonstrate that erythrocytes loaded with clodronate can also be effective in macrophage depletion. Here, clodronate was encapsulated in erythrocytes through hypotonic dialysis, isotonic resealing and reannealing to final concentrations of 4.1 ± 0.4 and 10.1 ± 0.8 μmol/ml of human and murine erythrocytes, respectively. The ability of clodronate-loaded erythrocytes to deplete macrophages was evaluated both in vitro and in vivo. In vitro studies on human macrophages showed that a single administration of engineered erythrocytes was able to reduce cell adherence capacity in a time-dependent manner, reaching 50 ± 4% reduction, 13 days post treatment. The administration of loaded erythrocytes to cultures of murine peritoneal macrophages was able to reduce macrophage adhesion 67 ± 3%, 48 h post treatment. In vivo, the ability of clodronate-loaded erythrocytes to deplete macrophages was evaluated both in Swiss and C57BL/6 mice. Swiss mice received 125 μg of clodronate through eryhtrocytes and 6 days post treatment 69 ± 7% reduction in the number of adherent peritoneal macrophages and 75 ± 5% reduction in number of spleen macrophages were observed. C57BL/6 mice received 220 μg clodronate by RBC and 3 and 8 days post treatment 65 ± 7% reduction in the number of spleen macrophages and the complete depletion of liver macrophages were obtained. In summary, our results indicate that clodronate selectively targeted to the phagocytic cells by a single administration of engineered erythrocytes is able to deplete macrophages, even if not completely. The transient suppression of macrophage functions through clodronate-loaded erythrocytes can be used in many biomedical phenomena and research applications.

Original languageEnglish
Pages (from-to)99-111
Number of pages13
JournalJournal of Drug Targeting
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • Autoimmune hemolytic anemia
  • Clodronate
  • Immunothrombocytopenia
  • Macrophages

ASJC Scopus subject areas

  • Pharmaceutical Science

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