Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection

Lipka, Jens; Semmler‐Behnke, Manuela; Sperling, Ralph A.; Wenk, Alexander; Takenaka, Shinji; Schleh, Carsten; Kissel, Thomas; Parak, Wolfgang J.; Kreyling, Wolfgang G.

doi:10.1016/j.biomaterials.2010.05.009

Cited by 458 publications

(363 citation statements)

References 42 publications

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“…However, knowledge on how these peptides interact and pack on a NP surface and how their anchorage affects molecular recognition of the biological target and the stability of the NPs is still scarce [19]. Studies on PEG-coated AuNPs biodistribution have shown that these NPs exhibit longer blood circulation times both in mice [13,14,20,21] and in rats [22] compared to their uncoated counterparts. Nevertheless, liver and spleen remained the preferential sites of the accumulation of the PEG-AuNPs.…”

Section: Introductionmentioning

confidence: 99%

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

Morais

Soares

Duarte

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tSuccessful application of gold nanoparticles (AuNPs) in biomedicine requires extensive safety assessment for which biokinetic studies are crucial.We evaluated the biodistribution of AuNPs ($20 nm) with different surface coatings: citrate, 11-MUA and 3 pentapeptides, CALNN, CALND and CALNS, after i.v. administration to rats (0.6-1 mg Au/kg). Biodistribution was evaluated based on Au tissue content measured by GFAAS.Citrate-AuNPs were rapidly removed from circulation with 60% of the injected dose depositing in the liver. Thirty minutes post-injection, the lungs presented about 6% of the injected dose with levels decreasing to 0.7% at 24 h. Gold levels in the spleen were of 2.6%. After 24 h, liver presented the highest Au level, followed by spleen and blood.A similar biodistribution profile was observed for MUA-coated AuNPs compared to Cit-AuNPs at 24 h post-injection, while significantly higher levels of peptide-capped AuNPs were found in the liver (74-86%) accompanied by a corresponding decrease in blood levels.TEM analysis of liver slices showed AuNPs in Kupffer cells and hepatocytes, trapped inside endosomes. Our data demonstrate that AuNPs are rapidly distributed and that the liver is the preferential accumulation organ. Peptide capping significantly increased hepatic uptake, showing the influence of AuNPs functionalization in biodistribution.

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Section: Introductionmentioning

confidence: 99%

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

Morais

Soares

Duarte

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

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“…Thirty minutes later the lungs were fixed with 2.5 % glutaraldehyde by vascular perfusion [8], removed, and processed for paraffin embedding as described recently [9,10]. All experiments were conducted under German federal guidelines for the use and care of laboratory animals and were approved by the Government of the District of Upper Bavaria and by the Institutional Animal Care and Use Committee of the Helmholtz Center Munich.…”

Section: Methodsmentioning

confidence: 99%

High-Resolution Phase-Contrast Imaging of Submicron Particles in Unstained Lung Tissue

Schittny¹,

Barré²,

Haberthür³

et al. 2011

AIP Conference Proceedings

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Abstract.To access the risks and chances of deposition of submicron particles in the gas-exchange area of the lung, a precise three-dimensional (3D)-localization of the sites of deposition is essential-especially because local peaks of deposition are expected in the acinar tree and in individual alveoli. In this study we developed the workflow for such an investigation. We administered 200-nm gold particles to young adult rats by intratracheal instillation. After fixation and paraffin embedding, their lungs were imaged unstained using synchrotron radiation x-ray tomographic microscopy (SRXTM) at the beamline TOMCAT (Swiss Light Source, Villigen, Switzerland) at sample detector distances of 2.5 mm (absorption contrast) and of 52.5 mm (phase contrast). A segmentation based on a global threshold of grey levels was successfully done on absorption-contrast images for the gold and on the phase-contrast images for the tissue. The smallest spots containing gold possessed a size of 1-2 voxels of 370-nm side length. We conclude that a combination of phase and absorption contrast SRXTM imaging is necessary to obtain the correct segmentation of both tissue and gold particles. This method will be used for the 3D localization of deposited particles in the gas-exchange area of the lung.

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“…Although effects of PEGylation regarding the translocation across the air-blood-barrier have not been investigated, yet, the fact that PEG surface modification decreases the macrophages uptake and cellular uptake result in an increase of the availability of free NPs on the epithelial cells of lung (Malugin & Ghandehari, 2010;Lipka et al, 2010). Besides, high drug accumulation in heart was observed in both groups.…”

Section: Biodistribution Studymentioning

confidence: 99%

Novel PEG-grafted nanostructured lipid carrier for systematic delivery of a poorly soluble anti-leukemia agent Tamibarotene: characterization and evaluation

et al. 2014

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The School of Pharmaceutical Science, Shandong University, Ji'nan, Shandong Province, PR China Abstract Tamibarotene (Am80), a poorly water-soluble drug for the treatment of acute promyelocytic leukemia (APL), loaded nanostructured lipid carrier (Am80-NLC) was developed and characterized previously. The purpose of the present work was to develop PEGylated nanostructured lipid carrier (PEG-NLC) for intravenous delivery of Am80, with the aim to further extend the circulation in blood and decrease the adverse events. Am80-loaded PEG-NLC (Am80-PEG-NLC) modified with PEG-40 stearate (PEG40-SA, molecular weight 2000 Da) was formulated by the method of melt-emulsification and low temperature-solidification technique. Am80-NLC was developed as well as control. Based on the optimized results of single-factor screening experiment, the average drug entrapment efficiency, the mean particle size, and zeta potential of Am80-NLC and Am80-PEG-NLC were found to be 89.8-94.3%, 178.9-201.6 nm, and À37.74 to À20.1 mV, respectively. In vitro drug release of Am80-NLC and Am80-PEG-NLC possessed a sustained release characteristic and their release behavior was in accordance with the Ritger-Peppas equation. In vivo, after intravenous (i.v.) injection to rats, the mean residence time (MRT) of Am80-PEG-NLC group was significantly prolonged and the AUC value was improved as well compared with the Am80-NLC group. Furthermore, the biodistribution in mice showed that Am80-PEG-NLC preferentially decreased the accumulation of Am80 in kidney and increased the drug concentration in brain after i.v. injection. In conclusion, Am80-PEG-NLC may be a potential delivery system for Am80 in the treatment of APL.

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Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection

Cited by 458 publications

References 42 publications

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

High-Resolution Phase-Contrast Imaging of Submicron Particles in Unstained Lung Tissue

Novel PEG-grafted nanostructured lipid carrier for systematic delivery of a poorly soluble anti-leukemia agent Tamibarotene: characterization and evaluation

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