Dose ranging, expanded acute toxicity and safety pharmacology studies for intravenously administered functionalized graphene nanoparticle formulations

Kanakia, Shruti; Toussaint, J; Chowdhury, Sayan Mullick; Tembulkar, Tanuf; Lee, Stephen; Jiang, Yaping; Lin, Richard Z.; Shroyer, Kenneth R.; Moore, William S.; Sitharaman, Balaji

doi:10.1016/j.biomaterials.2014.04.066

Cited by 126 publications

(110 citation statements)

References 46 publications

(79 reference statements)

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“…al. have evaluated the histopathology and biodistribution of GNP-Dex administered via intravenous injections in male Wistar rats at doses between 1–500 mg/kg after 1 and 30 days [104]. The results show that the maximum tolerable dose (MTD) of GNP-Dex is between 50–125 mg/kg.…”

Section: In Vivo Toxicologymentioning

confidence: 99%

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Toxicology of graphene-based nanomaterials

Lalwani

D’Agati

Khan

et al. 2016

Advanced Drug Delivery Reviews

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249

151

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Graphene based nanomaterials possess remarkable physiochemical properties suitable for diverse applications in electronics, telecommunications, energy and healthcare. The human and environmental exposure to graphene-based nanomaterials is increasing due to advancements in the synthesis, characterization and large-scale production of graphene and the subsequent development of graphene based biomedical and consumer products. A large number of in vitro and in vivo toxicological studies have evaluated the interactions of graphene-based nanomaterials with various living systems such as microbes, mammalian cells, and animal models. A significant number of studies have examined the short- and long-term in vivo toxicity and biodistribution of graphene synthesized by variety of methods and starting materials. A key focus of these examinations is to properly associate the biological responses with chemical and morphological properties of graphene. Several studies also report the environmental and genotoxicity response of pristine and functionalized graphene. This review summarizes these in vitro and in vivo studies and critically examines the methodologies used to perform these evaluations. Our overarching goal is to provide a comprehensive overview of the complex interplay of biological responses of graphene as a function of their physio-chemical properties.

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Section: In Vivo Toxicologymentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Toxicology of graphene-based nanomaterials

Lalwani

D’Agati

Khan

et al. 2016

Advanced Drug Delivery Reviews

Self Cite

249

151

View full text Add to dashboard Cite

show abstract

“…65 At this level, the amount administered was in the safety dose range for graphenic systems that could extend up to 50 mg/Kg body weight. [65][66][67][68][69] To the best of our knowledge, pristine graphene has never been used for in vivo PA imaging. In this work, our preliminary real time in vivo PAI study using a hybrid pristine graphene/PVA microbubble system shows the induced PA signal enhancement; 30 µl G/PVA (3×10 7 MBs/mL, graphene content 5 % w/w) being injected into wild mouse hind limb muscle.…”

Section: Ultrasound Properties Of G/pva Mbs: Ultrasonic Attenuation Imentioning

confidence: 98%

Graphene Meets Microbubbles: A Superior Contrast Agent for Photoacoustic Imaging

Toumia

Domenici

Orlanducci

et al. 2016

ACS Appl. Mater. Interfaces

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Coupling graphene with a soft polymer surface offers the possibility to build hybrid constructs with new electrical, optical, and mechanical properties. However, the low reactivity of graphene is a hurdle in the synthesis of such systems which is often bypassed by oxidizing its carbon planar structure. However, the defects introduced with this process jeopardize the properties of graphene. In this paper we present a different approach, applicable to many different polymer surfaces, which uses surfactant assisted ultrasonication to exfoliate, and simultaneously suspend, graphene in water in its intact form. Tethering pristine graphene sheets to the surfaces is accomplished by using suitable reactive functional groups of the surfactant scaffold. We focused on applying this approach to the fabrication of a hybrid system, made of pristine graphene tethered to poly(vinyl alcohol) based microbubbles (PVA MBs), designed for enhancing photoacoustic signals. Photoacoustic imaging (PAI) is a powerful preclinical diagnostic tool which provides real time images at a resolution of 40 μm. The leap toward clinical imaging has so far been hindered by the limited tissues penetration of near-infrared (NIR) pulsed laser radiation. Many academic and industrial research laboratories have met this challenge by designing devices, each with pros and cons, to enhance the photoacoustic (PA) signal. The major advantages of the hybrid graphene/PVA MBs construct, however, are (i) the preservation of graphene properties, (ii) biocompatibility, a consequence of the robust anchoring of pristine graphene to the bioinert surface of the PVA bubble, and (iii) a very good enhancement in a NIR spectral region of the PA signal, which does not overlap with the signals of PA active endogenous molecules such as hemoglobin.

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“…Histological assessment of the tissue sections was performed by an experienced diagnostic and research anatomic pathologist. 19) Data Analysis All the data are expressed as the mean±standard deviation (S.D.) unless particularly outlined.…”

Section: )mentioning

confidence: 99%

Docetaxel-Loaded Lecithoid Nanoparticles with Enhanced Lung Targeting Efficiency and Reduced Systemic Toxicity: Developed by Solid Dispersion and Effervescent Techniques

Zhang

Liu

Cheng

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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The application of chemotherapeutics with chemical drugs is always challenged by their high toxicities throughout the body in clinical trials. Here, we reported a smart formulation of docetaxel developed by solid dispersion and effervescent techniques for efficient and safe delivery of chemical drug to lung tissue. To achieve a high delivery to lung with reduced systemic toxicity, docetaxel was loaded into a kind of lecithoid nanoparticles (DTX-LN) which were prepared by a solid dispersion and effervescent method. After intravenous administration of DTX-LN to rabbit, the docetaxel level in lung was approximately 37-fold higher than that of docetaxel injection (DTX-INJ, a commercial injection preparation of DTX/polysorbate 80 micelles) group at 0.5 h and showed the highest tissue distribution among all the organs. Besides, the targeting parameter R e value of total increased amount of DTX in lung (AUC 0-t ) ratio (DTX-LN to DTX-INJ) is about 16.69, indicating a significantly enhanced lung targeting ability of DTX-LN. In subacute toxicity study, DTX-LN displayed a reduced hematotoxicity, especially for the negative impacts on white blood cells, lymphocyte and granulocyte when compared with DTX-INJ during both weekly and 3-weekly schedules administration. In addition, histopathological analysis demonstrated that DTX-LN showed less tissue damages on rabbit heart and kidney compared to DTX-INJ. Hence, this work would provide an insight for improving lung delivery efficacy of drugs with reduced systemic toxicity. Key words lecithoid nanoparticle; lung targeting; docetaxel; solid dispersionChemotherapy with cytotoxic drugs represents one of the major categories of therapeutic regimen for many kinds of cancers. However, the therapeutic activities of most anticancer drugs in clinical use are limited by their concomitant side effects for which these cytotoxic drugs always lack of the capability of discriminating the targeted tissues from the normal counterparts. 1) Docetaxel (DTX), a potent inhibitor of cell division, is one of the most effective members of the taxane drug class that represents a major class of antitumor agents, 2) and also is one of the most extensive used antitumor drugs because of its broad spectrum of antitumor activity, including breast, lung, prostate, gastric, head and neck, and ovarian cancer.3) The anti-tumor potency of DTX is dose-dependent, 4) and the in vivo efficacy of DTX is highly related to its concentration in tumor lesion. However, pharmacokinetic studies revealed that docetaxel injection (DTX-INJ, docetaxel/ polysorbate80 micelles injection) showed a wide-spread tissue distribution throughout the whole body, and thus needed a relative high dose to maintain the therapeutic efficacy in clinic. 5)Furthermore, the accumulation of DTX in non-related tissues contributed to most of clinical adverse reactions reported in patients (e.g., febrile neutropenia, fluid retention, peripheral neurotoxicity and musculoskeletal toxicity).6,7) Besides, due to its poor solubility in aqueous phase, the solu...

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Dose ranging, expanded acute toxicity and safety pharmacology studies for intravenously administered functionalized graphene nanoparticle formulations

Cited by 126 publications

References 46 publications

Toxicology of graphene-based nanomaterials

Toxicology of graphene-based nanomaterials

Graphene Meets Microbubbles: A Superior Contrast Agent for Photoacoustic Imaging

Docetaxel-Loaded Lecithoid Nanoparticles with Enhanced Lung Targeting Efficiency and Reduced Systemic Toxicity: Developed by Solid Dispersion and Effervescent Techniques

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