Nanodetoxification: Emerging Role of Nanomaterials in Drug Intoxication Treatment

Graham, Lauren M.; Nguyen, Thao M.; Lee, Sang Bok

doi:10.2217/nnm.11.75

Cited by 38 publications

(28 citation statements)

References 55 publications

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“…The converse principle of biodetoxification by drug-scavenging-agents is of increasing interest to drug-delivery scientists based on the clinical utility of absorptive properties [3,4]. The need for efficient detoxification agents is clear as drug-overdoses account for thousands of deaths annually in the United-States [5] and around the world, most-often in a young and healthy population.…”

Section: Introductionmentioning

confidence: 99%

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

Fettiplace

Lis

Ripper

et al. 2015

Journal of Controlled Release

105

102

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Triglyceride micro-emulsions such as Intralipid® have been used to reverse cardiac toxicity induced by a number of drugs but reservations about their broad-spectrum applicability remain because of the poorly understood mechanism of action. Herein we report an integrated mechanism of reversal of bupivacaine toxicity that includes both transient drug scavenging and a cardiotonic effect that couple to accelerate movement of the toxin away from sites of toxicity. We thus propose a multi-modal therapeutic paradigm for colloidal bio-detoxification whereby a micro-emulsion both improves cardiac output and rapidly ferries the drug away from organs subject to toxicity. In vivo and in silico models of toxicity were combined to test the contribution of individual mechanisms and reveal the multi-modal role played by the cardiotonic and scavenging actions of the triglyceride suspension. These results suggest a method to predict which drug toxicities are most amenable to treatment and inform the design of next-generation therapeutics for drug overdose.

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Section: Introductionmentioning

confidence: 99%

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

Fettiplace

Lis

Ripper

et al. 2015

Journal of Controlled Release

105

102

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show abstract

“…The large surface area to volume ratio, specific loading capacity, prolonged circulation time, and biosafety of nanomaterials contribute to their possible beneficial effect as antidotes. 11 We had previously developed the nanoemulsions, which are termed squarticles, that contain squalene as the lipid cores and Pluronic F68/phosphatidylcholines as the emulsifiers for enhancing anti-alopecia drug uptake in hair follicles. 12 Squalene is a polyunsaturated hydrocarbon with a lipophilic character and high biocompatibility.…”

Section: Introductionmentioning

confidence: 99%

Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

Chen¹,

Huang²,

Elzoghby³

et al. 2017

IJN

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The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively. Through the entrapment study, squarticles could intercept 40%–50% of the amitriptyline during 2 h with low leakage after loading into the nanoparticles. The results of isothermal titration calorimetry demonstrated greater interaction of amitriptyline with the surface of anionic squarticles ( K a =28,700) than with cationic ones ( K a =5,010). Real-time imaging showed that intravenous administration of anionic squarticles resulted in a prolonged retention in the circulation. In a rat model of amitriptyline poisoning, anionic squarticles increased the plasma drug concentration by 2.5-fold. The drug uptake in the highly perfused organs was diminished after squarticle infusion, indicating the lipid sink effect of bringing the entrapped overdosed drug in the tissues back into circulation. In addition, the anionic nanosystems restored the mean arterial pressure to near normal after amitriptyline injection. The survival rate of overdosed amitriptyline increased from 25% to 75% by treatment with squarticles. Our results show that the adverse effects of amitriptyline intoxication could be mitigated by administering anionic squarticles. This lipid nanoemulsion is a potent antidote to extract amitriptyline and eliminate it.

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“…[33][34][35] Advances in nanotechnology design and delivery can allow delivery of a drug to a targeted tissue, release of a drug at a controlled rate, treatments for drug detoxification, 36 or detection of the early stages of a carcinogenic process. 37,38 For instance, Doxil ® and Abraxane ® are two nanodrugs already approved and currently available.…”

Section: Nanotechnology and Nanoinformaticsmentioning

confidence: 99%

Nanoinformatics: a new area of research in nanomedicine

Maojo¹,

Fritts²,

Iglesia³

et al. 2012

IJN

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Over a decade ago, nanotechnologists began research on applications of nanomaterials for medicine. This research has revealed a wide range of different challenges, as well as many opportunities. Some of these challenges are strongly related to informatics issues, dealing, for instance, with the management and integration of heterogeneous information, defining nomenclatures, taxonomies and classifications for various types of nanomaterials, and research on new modeling and simulation techniques for nanoparticles. Nanoinformatics has recently emerged in the USA and Europe to address these issues. In this paper, we present a review of nanoinformatics, describing its origins, the problems it addresses, areas of interest, and examples of current research initiatives and informatics resources. We suggest that nanoinformatics could accelerate research and development in nanomedicine, as has occurred in the past in other fields. For instance, biomedical informatics served as a fundamental catalyst for the Human Genome Project, and other genomic and -omics projects, as well as the translational efforts that link resulting molecular-level research to clinical problems and findings.

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Nanodetoxification: Emerging Role of Nanomaterials in Drug Intoxication Treatment

Cited by 38 publications

References 55 publications

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

Nanoinformatics: a new area of research in nanomedicine

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