Technetium-99m-labeled stealth pH-sensitive liposomes: a new strategy to identify infection in experimental model

Carmo, Vildete A.S.; Oliveira, Mônica Cristina; Mota, Luciene das Graças; Freire, Luís Paulo; Ferreira, Raphael L B; Cardoso, Valbert Nascimento

doi:10.1590/s1516-89132007000600025

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…Recently, Iman and colleagues ( 27 ) also investigated the distribution of LAmB and DAmB in L. major -infected BALB/c mice, but skin was not evaluated in this study. Increased accumulation of liposomes in inflammatory over healthy sites has also been described for subcutaneous tumors ( 28 ), bacterial skin abscesses ( 29 , 30 ), and fungal infections ( 31 ). The so-called enhanced permeation and retention effect, increased drug accumulation at sites of leaky vasculature and defective lymphatic drainage, has been coined as the rationale behind nanoparticle-based drug delivery in cancer and inflammation ( 16 ).…”

Section: Discussionmentioning

confidence: 90%

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

Wijnant

Bocxlaer

Yardley

et al. 2018

Antimicrob Agents Chemother

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AmBisome (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with those of the deoxycholate form of AmB (DAmB; trade name Fungizone) in murine models of Leishmania major CL. Drug levels at the target site (the localized lesion) 48 h after single intravenous (i.v.) dosing of the individual AmB formulations (1 mg/kg of body weight) were similar but were 3-fold higher for LAmB than for DAmB on day 10 after multiple administrations (1 mg/kg on days 0, 2, 4, 6, and 8). After single and multiple dosing, intralesional concentrations were 5- and 20-fold, respectively, higher than those in the healthy control skin of the same infected mice. We then evaluated how drug levels in the lesion after LAmB treatment relate to therapeutic outcomes. After five administrations of the drug at 0, 6.25, or 12.5 mg/kg (i.v.), there was a clear correlation between dose level, intralesional AmB concentration, and relative reduction in parasite load and lesion size (R2 values of >0.9). This study confirms the improved efficacy of the liposomal over the deoxycholate AmB formulation in experimental CL, which is related to higher intralesional drug accumulation.

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Section: Discussionmentioning

confidence: 90%

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

Wijnant

Bocxlaer

Yardley

et al. 2018

Antimicrob Agents Chemother

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“…These drug-delivery systems have proven to be interesting carriers of imaging agents to identify infectious sites, since these areas have high blood flow and permeability that allow for the liposomes to extravasate and accumulate. [13][14][15] Despite that, radiolabeled liposomes are not able to differentiate septic from aseptic inflammation. In an effort to overcome the lack of specificity of radiolabeled liposomes and to improve the image quality, our research group has previously developed pH-sensitive liposomes containing 99m technetium-radiolabeled CFT ( 99m Tc-CFT) for the diagnosis of bone infections.…”

mentioning

confidence: 99%

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

Ferreira¹,

Boratto²,

Cardoso³

et al. 2015

IJN

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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.

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“…However, Tc-99 m radiolabeled PC:SDC micelles can also be assumed as sensitive radiopharmaceutical agents due to the mechanism of imaging of infection and inflammation. 99m Tcradiolabeled, PEGylated, PC, SDC and DTPA-PE containing nanosized micelles can accumulate at infection and inflammation sites due to long vascular circulation of vesicles by small particle size and surface coating by an hydrophilic polymer (such as PEG) [47,[52][53][54]. It was reported in some previous studies that the accumulation of radiolabeled liposomes in at infectious sites is performed by leakage of the vesicles through vessels.…”

Section: In Vitro Bacterial Bindingmentioning

confidence: 99%

“…This leakage depends on the enhanced vascular permeability and following phagocythosis by macrophages of infected tissue. It was reported that the endothelial junctions existing in the blood vessel provides the penetration of the particles smaller than 200 nm from the vascularization [48,54]. Therefore, surface coated, nanosized drug delivery systems like liposomes can be accumulated at the site of infection and inflammation due to long circulation, enhanced vascular permeability and reduced removal by opsonisation [49,52,65].…”

Section: In Vitro Bacterial Bindingmentioning

confidence: 99%

“…Liposomes which are formulated in a particle size of nanometer range and surface coated for passive targeting are called stealth liposomes. A variety of stealth liposomes were prepared and evaluated for this purpose [49,[52][53][54]. Although many previous studies were performed for 99m Tc-radiolabeling of antibiotics and liposomes, these techniques are still very valuable for their accumulation in the site of the infection and inflammation [25].…”

Section: Introductionmentioning

confidence: 99%

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99mTc-radiolabeled Levofloxacin and micelles as infection and inflammation imaging agents

Silindir-Gunay

Özer

2020

Journal of Drug Delivery Science and Technology

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A B S T R A C T Easy and early detection of infection and inflammation is essential for early and effective treatment. In this study, PEGylated micelles were designed and both micelles and Levofloxacin were radiolabeled with 99m TcO 4 to develop potential radiotracers for detection of infection/inflammation. Radiolabeling efficiency, in vitro stability and bacterial binding of 99m Tc-Levofloxacin and 99m Tc-micelles were compared. The aim of this study is to formulate and compare 99m Tc-Levofloxacin and 99m Tc-micelles as infection and inflammation agents having different mechanisms for the accumulation at infection and inflammation site. PEGylated micelles were designed with a particle size of 80 ± 0.7 nm and proper characterization properties. High radiolabeling efficiency was achieved for 99m Tc-Levofloxacin (96%) and 99m Tc-micelles (87%). The radiolabeling efficiency was remained stable with some insignificant alterations for both radiotracers at 25°C for 24 h. Although in vitro bacterial binding of 99m Tc-levofloxacine was higher than 99m Tc-micelles, 99m Tc-micelles may also be evaluated potential agent due to long circulation and passive accumulation mechanisms at infection/inflammation site. Both radiopharmaceutical agents exhibit potential results in design, characterization, radiolabeling efficiency and in vitro bacterial binding point of view.

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Technetium-99m-labeled stealth pH-sensitive liposomes: a new strategy to identify infection in experimental model

Abstract: The diagnosis of inflammatory and infectious processes is an important goal in medicine. The use of radiopharmaceuticals for identification of inflammation and infection

Cited by 9 publications

References 20 publications

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

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

99mTc-radiolabeled Levofloxacin and micelles as infection and inflammation imaging agents

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