Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis

Diego dos Santos Ferreira,1 Fernanda Alves Boratto,1 Valbert Nascimento Cardoso,2 Rogéria Serakides,3 Simone Odília Fernandes,2 Lucas Antônio Miranda Ferreira,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy, 2Departm...

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Autores principales:	Ferreira DS, Boratto FA, Cardoso VN, Serakides R, Fernandes SO, Ferreira LAM, Oliveira MC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9acd3f25e66c4b4f8ca87c2d675cd1c3
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spelling	oai:doaj.org-article:9acd3f25e66c4b4f8ca87c2d675cd1c32021-12-02T07:46:15ZAlendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis1178-2013https://doaj.org/article/9acd3f25e66c4b4f8ca87c2d675cd1c32015-03-01T00:00:00Zhttp://www.dovepress.com/alendronate-coated-long-circulating-liposomes-containing-99mtechnetium-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Diego dos Santos Ferreira,1 Fernanda Alves Boratto,1 Valbert Nascimento Cardoso,2 Rogéria Serakides,3 Simone Odília Fernandes,2 Lucas Antônio Miranda Ferreira,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy, 2Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, 3Veterinary School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Abstract: Osteomyelitis is a progressive destruction of bones caused by microorganisms. Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the overall uptake. In this work, long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime were prepared and their ability to identify infectious foci (osteomyelitis) in animal models was evaluated. The effect of the presence of PEGylated lipids and surface-attached alendronate was evaluated. The bone-targeted long-circulating liposomal 99mtechnetium–ceftizoxime showed higher uptake in regions of septic inflammation than did the non-long-circulating and/or alendronate-non-coated liposomes, showing that both the presence of PEGylated lipids and alendronate coating are important to optimize the bone targeting. Scintigraphic images of septic or aseptic inflammation-bearing Wistar rats, as well as healthy rats, were acquired at different time intervals after the intravenous administration of these liposomes. The target-to-non-target ratio proved to be significantly higher in the osteomyelitis-bearing animals for all investigated time intervals. Biodistribution studies were also performed after the intravenous administration of the formulation in osteomyelitis-bearing animals. A significant amount of liposomes were taken up by the organs of the mononuclear phagocyte system (liver and spleen). Intense renal excretion was also observed during the entire experiment period. Moreover, the liposome uptake by the infectious focus was significantly high. These results show that long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime have a tropism for infectious foci. Keywords: bone targeting, radiolabeled antibiotics, scintigraphic imaging, bone infection diagnosisFerreira DSBoratto FACardoso VNSerakides RFernandes SOFerreira LAMOliveira MCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2441-2450 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Ferreira DS Boratto FA Cardoso VN Serakides R Fernandes SO Ferreira LAM Oliveira MC Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis
description	Diego dos Santos Ferreira,1 Fernanda Alves Boratto,1 Valbert Nascimento Cardoso,2 Rogéria Serakides,3 Simone Odília Fernandes,2 Lucas Antônio Miranda Ferreira,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy, 2Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, 3Veterinary School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Abstract: Osteomyelitis is a progressive destruction of bones caused by microorganisms. Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the overall uptake. In this work, long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime were prepared and their ability to identify infectious foci (osteomyelitis) in animal models was evaluated. The effect of the presence of PEGylated lipids and surface-attached alendronate was evaluated. The bone-targeted long-circulating liposomal 99mtechnetium–ceftizoxime showed higher uptake in regions of septic inflammation than did the non-long-circulating and/or alendronate-non-coated liposomes, showing that both the presence of PEGylated lipids and alendronate coating are important to optimize the bone targeting. Scintigraphic images of septic or aseptic inflammation-bearing Wistar rats, as well as healthy rats, were acquired at different time intervals after the intravenous administration of these liposomes. The target-to-non-target ratio proved to be significantly higher in the osteomyelitis-bearing animals for all investigated time intervals. Biodistribution studies were also performed after the intravenous administration of the formulation in osteomyelitis-bearing animals. A significant amount of liposomes were taken up by the organs of the mononuclear phagocyte system (liver and spleen). Intense renal excretion was also observed during the entire experiment period. Moreover, the liposome uptake by the infectious focus was significantly high. These results show that long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime have a tropism for infectious foci. Keywords: bone targeting, radiolabeled antibiotics, scintigraphic imaging, bone infection diagnosis
format	article
author	Ferreira DS Boratto FA Cardoso VN Serakides R Fernandes SO Ferreira LAM Oliveira MC
author_facet	Ferreira DS Boratto FA Cardoso VN Serakides R Fernandes SO Ferreira LAM Oliveira MC
author_sort	Ferreira DS
title	Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis
title_short	Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis
title_full	Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis
title_fullStr	Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis
title_full_unstemmed	Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis
title_sort	alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/9acd3f25e66c4b4f8ca87c2d675cd1c3
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Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis

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