In vivo evaluation of safety, biodistribution and pharmacokinetics of laser-synthesized gold nanoparticles

Abstract Capable of generating plasmonic and other effects, gold nanostructures can offer a variety of diagnostic and therapy functionalities for biomedical applications, but conventional chemically-synthesized Au nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au nanoparticles (AuNP) present a viable alternative to chemical counterparts and can offer exceptional purity (no trace of contaminants) and unusual surface chemistry making possible direct conjugation with biocompatible polymers (dextran, polyethylene glycol). This work presents the first pharmacokinetics, biodistribution and safety study of laser-ablated dextran-coated AuNP (AuNPd) under intravenous administration in small animal model. Our data show that AuNPd are rapidly eliminated from the blood circulation and accumulated preferentially in liver and spleen, without inducing liver or kidney toxicity, as confirmed by the plasmatic ALAT and ASAT activities, and creatininemia values. Despite certain residual accumulation in tissues, we did not detect any sign of histological damage or inflammation in tissues, while IL-6 level confirmed the absence of any chronic inflammation. The safety of AuNPd was confirmed by healthy behavior of animals and the absence of acute and chronic toxicities in liver, spleen and kidneys. Our results demonstrate that laser-synthesized AuNP are safe for biological systems, which promises their successful biomedical applications.

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In vivo functional chronic imaging of a small animal model using optical-resolution photoacoustic microscopy

Medical Physics ◽

10.1118/1.3137572 ◽

2009 ◽

Vol 36 (6Part1) ◽

pp. 2320-2323 ◽

Cited By ~ 42

Author(s):

Song Hu ◽

Konstantin Maslov ◽

Lihong V. Wang

Keyword(s):

Animal Model ◽

Optical Resolution ◽

Small Animal ◽

Photoacoustic Microscopy ◽

Small Animal Model

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Polysialic Acid Modified Liposomes for Improving Pharmacokinetics and Overcoming Accelerated Blood Clearance Phenomenon

Coatings ◽

10.3390/coatings10090834 ◽

2020 ◽

Vol 10 (9) ◽

pp. 834

Author(s):

Xi Han ◽

Ting Zhang ◽

Mengyang Liu ◽

Yanzhi Song ◽

Xinrong Liu ◽

...

Keyword(s):

Blood Circulation ◽

Polysialic Acid ◽

Repeated Administration ◽

The Body ◽

Circulation Time ◽

Blood Clearance ◽

In Vivo Evaluation ◽

Accelerated Blood Clearance ◽

Abc Phenomenon

Poly (ethylene glycol) (PEG) modified nanocarriers are being used widely in the drug delivery system (DDS). However, the “accelerated blood clearance (ABC) phenomenon” was induced upon repeated administration of PEG-modified liposomes, resulting in reduced blood circulation time, and increased accumulation in liver and spleen. To avoid the unexpected phenomenon, polysialic acid (PSA) was selected to modify liposomes. PSA is a natural, highly hydrophilic polysaccharide polymer for which no receptors exists in the body. It is non-immunogenic, biodegradable and endows the conjugated bioactive macromolecule and drugs with increased circulation time in vivo. In the present study, the in vivo evaluation showed that PSA modified liposomes (PSA-Lip) afford extended blood circulation in wistar rats and beagle dogs. Moreover, the ABC phenomenon did not occur and the IgM antibody was not induced after repeated injections of PSA-Lip. These results strongly suggest that PSA modification represents a promising strategy to afford good stealth of the liposomes without evoking the ABC phenomenon.

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In vivo evaluation of whey protein-based biofilms as scaffolds for cutaneous cell cultures and biomedical applications

Biomedical Materials ◽

10.1088/1748-6041/2/1/s06 ◽

2007 ◽

Vol 2 (1) ◽

pp. S38-S44 ◽

Cited By ~ 7

Author(s):

Mahmoud Rouabhia ◽

Vanessa Gilbert ◽

Hongxum Wang ◽

Muriel Subirade

Keyword(s):

Whey Protein ◽

Cell Cultures ◽

Biomedical Applications ◽

In Vivo Evaluation ◽

Cutaneous Cell

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Longitudinal in vivo transcutaneous observation of Raman signals from breast cancer during chemotherapy in small animal model

10.1117/12.2079279 ◽

2015 ◽

Author(s):

Myeongsu Seong ◽

NoSoung Myoung ◽

Sang-Youp Yim ◽

Jae G. Kim

Keyword(s):

Breast Cancer ◽

Animal Model ◽

Small Animal ◽

Small Animal Model

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Development and Characterization of a Guinea Pig-Adapted Sudan Virus

Journal of Virology ◽

10.1128/jvi.02331-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 392-399 ◽

Cited By ~ 23

Author(s):

Gary Wong ◽

Shihua He ◽

Haiyan Wei ◽

Andrea Kroeker ◽

Jonathan Audet ◽

...

Keyword(s):

Animal Model ◽

Guinea Pig ◽

Guinea Pigs ◽

Lethal Dose ◽

Fatal Outcome ◽

Small Animal ◽

Disease Outbreak ◽

Small Animal Model ◽

Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

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Processing, Characterization, and in Vivo Evaluation of Poly(l-lactic acid)-Fish Gelatin Electrospun Membranes for Biomedical Applications

ACS Applied Bio Materials ◽

10.1021/acsabm.8b00023 ◽

2018 ◽

Vol 1 (2) ◽

pp. 226-236

Author(s):

Mariana Branco ◽

Ana R. Caseiro ◽

Dina M. Silva ◽

Irina Amorim ◽

Alexandra Rêma ◽

...

Keyword(s):

Lactic Acid ◽

Biomedical Applications ◽

Fish Gelatin ◽

In Vivo Evaluation ◽

Electrospun Membranes

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Nanocomposite Films of Chitosan-Grafted Carbon Nano-Onions for Biomedical Applications

Molecules ◽

10.3390/molecules25051203 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1203 ◽

Cited By ~ 2

Author(s):

Carlos David Grande Tovar ◽

Jorge Iván Castro ◽

Carlos Humberto Valencia ◽

Diana Paola Navia Porras ◽

José Herminsul Mina Hernandez ◽

...

Keyword(s):

Polyvinyl Alcohol ◽

Biomedical Applications ◽

Wistar Rats ◽

Carbon Nanomaterials ◽

Biological Properties ◽

High Rate ◽

Nanocomposite Films ◽

Scanning Calorimetry ◽

In Vivo Evaluation

The design of scaffolding from biocompatible and resistant materials such as carbon nanomaterials and biopolymers has become very important, given the high rate of injured patients. Graphene and carbon nanotubes, for example, have been used to improve the physical, mechanical, and biological properties of different materials and devices. In this work, we report the grafting of carbon nano-onions with chitosan (CS-g-CNO) through an amide-type bond. These compounds were blended with chitosan and polyvinyl alcohol composites to produce films for subdermal implantation in Wistar rats. Films with physical mixture between chitosan, polyvinyl alcohol, and carbon nano-onions were also prepared for comparison purposes. Film characterization was performed with Fourier Transformation Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Tensile strength, X-ray Diffraction Spectroscopy (XRD), and Scanning Electron Microscopy (SEM). The degradation of films into simulated body fluid (SBF) showed losses between 14% and 16% of the initial weight after 25 days of treatment. Still, a faster degradation (weight loss and pH changes) was obtained with composites of CS-g-CNO due to a higher SBF interaction by hydrogen bonding. On the other hand, in vivo evaluation of nanocomposites during 30 days in Wistar rats, subdermal tissue demonstrated normal resorption of the materials with lower inflammation processes as compared with the physical blends of ox-CNO formulations. SBF hydrolytic results agreed with the in vivo degradation for all samples, demonstrating that with a higher ox-CNO content increased the stability of the material and decreased its degradation capacity; however, we observed greater reabsorption with the formulations including CS-g-CNO. With this research, we demonstrated the future impact of CS/PVA/CS-g-CNO nanocomposite films for biomedical applications.

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Radiolabeled Molecular Imaging Probes for the In Vivo Evaluation of Cellulose Nanocrystals for Biomedical Applications

Biomacromolecules ◽

10.1021/acs.biomac.8b01313 ◽

2018 ◽

Vol 20 (2) ◽

pp. 674-683 ◽

Cited By ~ 9

Author(s):

Surachet Imlimthan ◽

Sofia Otaru ◽

Outi Keinänen ◽

Alexandra Correia ◽

Kalle Lintinen ◽

...

Keyword(s):

Molecular Imaging ◽

Cellulose Nanocrystals ◽

Biomedical Applications ◽

In Vivo Evaluation ◽

Molecular Imaging Probes ◽

Imaging Probes

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Pharmacokinetics, Biodistribution, and Biosafety of PEGylated Gold Nanoparticles In Vivo

Nanomaterials ◽

10.3390/nano11071702 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1702

Author(s):

Katarina Kozics ◽

Monika Sramkova ◽

Kristina Kopecka ◽

Patricia Begerova ◽

Alena Manova ◽

...

Keyword(s):

Gold Nanoparticles ◽

Blood Circulation ◽

Biomedical Applications ◽

Kidney Cells ◽

Monocyte Count ◽

Time Intervals ◽

Dna Breakage ◽

Toxicological Data ◽

Time Point

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat’s liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects.

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