Technetium-99m-labeled ceftizoxime loaded long-circulating and pH-sensitive liposomes used to identify osteomyelitis

Ferreira, Soraya Maria Zandim Maciel Dias; Domingos, Giselle Pires; Ferreira, Diêgo S.; Rocha, Talita Guieiro Ribeiro; Serákides, Rogéria; Rezende, Cleuza Maria de Faria; Cardoso, Valbert Nascimento; Fernandes, Simone Odília Antunes; Oliveira, Mônica Cristina

doi:10.1016/j.bmcl.2012.05.105

Cited by 22 publications

(16 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This formulation demonstrated higher affinity for infectious sites than inflamed tissues, although the uptake was not increased, compared to the free 99m Tc-CFT. 16 The explanation could be related to the fact that bones are poorly vascularized and composed mainly of mineral matrixes, which prevent most substances from reaching the region. 17 In light of this, the development of a surface-modified liposome by the incorporation of a ligand with high affinity for regions of intense bone turnover may be a promising strategy to increase the uptake of 99m Tc-CFT at these regions and, consequently, improve the image quality.…”

mentioning

confidence: 99%

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

Ferreira¹,

Boratto²,

Cardoso³

et al. 2015

IJN

Self Cite

View full text Add to dashboard Cite

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 99m technetium-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 99m technetium–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 99m technetium-radiolabeled ceftizoxime have a tropism for infectious foci.

show abstract

mentioning

confidence: 99%

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

Ferreira¹,

Boratto²,

Cardoso³

et al. 2015

IJN

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ferreira et al (2012 developed long-circulating and pH-sensitive liposomes containing a 99mTc-labeled antibiotic, ceftizoxime, SpHL-(99mTc-CF) to identify osteomyelitis, an infectious disease located in the bone or bone marrow. The biodistribution studies showed a high values in the target-non target ratio and indicated that SpHL-99mTc-CF as a potential agent for the diagnosis of bone infections (Ferreira et al, 2012).…”

Section: The Ph-sensitive Liposomes In Tumor Diagnosismentioning

confidence: 95%

“…The leakage of the imaging reporter from the vesicles was associated with a relativity enhancement that allowed its visualization by MRI. It was claimed that the release mechanism implies the protonation of the basic sites that leads to vesicle aggregation, thus enabling the expression of the fusogenic property (Torres et al, 2011). Ferreira et al (2012 developed long-circulating and pH-sensitive liposomes containing a 99mTc-labeled antibiotic, ceftizoxime, SpHL-(99mTc-CF) to identify osteomyelitis, an infectious disease located in the bone or bone marrow.…”

Section: The Ph-sensitive Liposomes In Tumor Diagnosismentioning

confidence: 99%

A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery

2014

View full text Add to dashboard Cite

The pH-sensitive liposomes have been extensively used as an alternative to conventional liposomes in effective intracellular delivery of therapeutics/antigen/DNA/diagnostics to various compartments of the target cell. Such liposomes are destabilized under acidic conditions of the endocytotic pathway as they usually contain pH-sensitive lipid components. Therefore, the encapsulated content is delivered into the intracellular bio-environment through destabilization or its fusion with the endosomal membrane. The therapeutic efficacy of pHsensitive liposomes enables them as biomaterial with commercial utility especially in cancer treatment. In addition, targeting ligands including antibodies can be anchored on the surface of pH-sensitive liposomes to target specific cell surface receptors/antigen present on tumor cells. These vesicles have also been widely explored for antigen delivery and serve as immunological adjuvant to enhance the immune response to antigens. The present review deals with recent research updates on application of pH-sensitive liposomes in chemotherapy/ diagnostics/antigen/gene delivery etc.

show abstract

“…Osteomyelitis [1] is a bone infectious disease caused by the invasion of bacteria or fungi, [5][6][7] Recently, nanomedicine has attracted a lot of attention in that the nano-sized carrier can deliver drug molecules to specific site of interest with the aid of targeting moiety and achieve sustained release, resulting in improved therapeutic effect and reduced side effect. However, the presence of "blood-bone barrier" [8] make it less efficient to deliver drugs to bone lesion sites.…”

Section: Introductionmentioning

confidence: 99%

Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin

Cong

Quan

Liu

et al. 2015

Journal of Biomaterials Science, Polymer Edition

View full text Add to dashboard Cite

Osteomyelitis is a bone infection disease which is caused by bacteria or other germs, and could cause serious impact on the health and working capacity of the patients. Alendronate (ALN) can chelate strongly with the calcium ion of hydroxyapatite (HA) which is commonly used to treat osteoporosis. Nanomedicine has attracted a lot of attention in that the nano-sized carrier can deliver drug molecules to specific site of interest with the aid of targeting moiety and achieve sustained release, resulting in improved therapeutic effect and reduced side effect. In this study, micelles self-assembled from poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-alendronate (PLGA-PEG-ALN) copolymer were prepared for bone-targeted delivery of vancomycin (Van). The chemical structure of PLGA-PEG-ALN was confirmed by proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. The formation of the nanoparticles was characterized by dynamic light scattering, transmission electronic microscopy as well as the critical micelle concentration measurement. Release profiles from the micelles revealed that the conjugation of ALN to the surface of micelle did not pose adverse effect on the drug-loading capacity and release behaviors. The cytotoxicity of Van-loaded PLGA-PEG-ALN micelles as well as the blank micelles was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay toward rat bone marrow stromal cells (rBMSCs) and human embryonic hepatocytes (L02 cells), and results showed that this Van-loaded micelle possesses appropriate cytotoxicity and is safe in the potential treatment of osteomyelitis. The in vitro affinity of PLGA-PEG-ALN micelles to the HA was also confirmed in vitro. The antibacterial effect of Van-loaded PLGA-PEG-ALN micelles was tested against Staphylococcus aureus (SA) which is the main pathogenic bacteria in osteomyelitis, and the results showed that the Van-loaded micelles can effectively inhibit the growth of SA. These results demonstrated that the PLGA-PEG-ALN micelles may be potentially used for the bone targeted delivery of Van.

show abstract

Technetium-99m-labeled ceftizoxime loaded long-circulating and pH-sensitive liposomes used to identify osteomyelitis

Cited by 22 publications

References 12 publications

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

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

A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery

Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin

Contact Info

Product

Resources

About