Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.

Bisphosphonates, besides being important drugs for the treatment of various bone diseases, could also be used to induce apoptosis in macrophage-like and cancer cells. However, their activity in vivo is limited by a short plasma half-life and rapid uptake within bone. Therefore, several delivery syst...

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Autores principales:	Raffaella Sabatino, Antonella Antonelli, Serafina Battistelli, Reto Schwendener, Mauro Magnani, Luigia Rossi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56be3593f83b4891b7e1e408295e6da1
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spelling	oai:doaj.org-article:56be3593f83b4891b7e1e408295e6da12021-11-11T08:21:20ZMacrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.1932-620310.1371/journal.pone.0101260https://doaj.org/article/56be3593f83b4891b7e1e408295e6da12014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24968029/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Bisphosphonates, besides being important drugs for the treatment of various bone diseases, could also be used to induce apoptosis in macrophage-like and cancer cells. However, their activity in vivo is limited by a short plasma half-life and rapid uptake within bone. Therefore, several delivery systems have been proposed to modify their pharmacokinetic profile and biodistribution. Among these, red blood cells (RBCs) represent one of the most promising biological carriers. The aim of this study was to select the best performing compound among Clodronate, Pamidronate, Ibandronate and Zoledronate in killing macrophages and to investigate RBCs as innovative carrier system to selectively target bisphosphonates to macrophages. To this end, the encapsulation of the selected bisphosphonates in autologous RBCs as well as the effect on macrophages, both in vitro and in vivo were studied. This work shows that, among the tested bisphosphonates, Zoledronate has proven to be the most active molecule. Human and murine RBCs have been successfully loaded with Zoledronate by a procedure of hypotonic dialysis and isotonic resealing, obtaining a dose-dependent drug entrapment with a maximal loading of 7.96±2.03, 6.95±3.9 and 7.0±1.89 µmoles of Zoledronate/ml of packed RBCs for human, Swiss and Balb/C murine RBCs, respectively. Engineered RBCs were able to detach human and murine macrophages in vitro, leading to a detachment of 66±8%, 67±8% and 60.5±3.5% for human, Swiss and Balb/C RBCs, respectively. The in vivo efficacy of loaded RBCs was tested in Balb/C mice administering 59 µg/mouse of RBC-encapsulated Zoledronate. By a single administration, depletion of 29.0±16.38% hepatic macrophages and of 67.84±5.48% spleen macrophages was obtained, confirming the ability of encapsulated Zoledronate to deplete macrophages in vivo. In conclusion, RBCs loaded with Zoledronate should be considered a suitable system for targeted delivery to macrophages, both in vitro and in vivo.Raffaella SabatinoAntonella AntonelliSerafina BattistelliReto SchwendenerMauro MagnaniLuigia RossiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e101260 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raffaella Sabatino Antonella Antonelli Serafina Battistelli Reto Schwendener Mauro Magnani Luigia Rossi Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
description	Bisphosphonates, besides being important drugs for the treatment of various bone diseases, could also be used to induce apoptosis in macrophage-like and cancer cells. However, their activity in vivo is limited by a short plasma half-life and rapid uptake within bone. Therefore, several delivery systems have been proposed to modify their pharmacokinetic profile and biodistribution. Among these, red blood cells (RBCs) represent one of the most promising biological carriers. The aim of this study was to select the best performing compound among Clodronate, Pamidronate, Ibandronate and Zoledronate in killing macrophages and to investigate RBCs as innovative carrier system to selectively target bisphosphonates to macrophages. To this end, the encapsulation of the selected bisphosphonates in autologous RBCs as well as the effect on macrophages, both in vitro and in vivo were studied. This work shows that, among the tested bisphosphonates, Zoledronate has proven to be the most active molecule. Human and murine RBCs have been successfully loaded with Zoledronate by a procedure of hypotonic dialysis and isotonic resealing, obtaining a dose-dependent drug entrapment with a maximal loading of 7.96±2.03, 6.95±3.9 and 7.0±1.89 µmoles of Zoledronate/ml of packed RBCs for human, Swiss and Balb/C murine RBCs, respectively. Engineered RBCs were able to detach human and murine macrophages in vitro, leading to a detachment of 66±8%, 67±8% and 60.5±3.5% for human, Swiss and Balb/C RBCs, respectively. The in vivo efficacy of loaded RBCs was tested in Balb/C mice administering 59 µg/mouse of RBC-encapsulated Zoledronate. By a single administration, depletion of 29.0±16.38% hepatic macrophages and of 67.84±5.48% spleen macrophages was obtained, confirming the ability of encapsulated Zoledronate to deplete macrophages in vivo. In conclusion, RBCs loaded with Zoledronate should be considered a suitable system for targeted delivery to macrophages, both in vitro and in vivo.
format	article
author	Raffaella Sabatino Antonella Antonelli Serafina Battistelli Reto Schwendener Mauro Magnani Luigia Rossi
author_facet	Raffaella Sabatino Antonella Antonelli Serafina Battistelli Reto Schwendener Mauro Magnani Luigia Rossi
author_sort	Raffaella Sabatino
title	Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
title_short	Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
title_full	Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
title_fullStr	Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
title_full_unstemmed	Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
title_sort	macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/56be3593f83b4891b7e1e408295e6da1
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Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.

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