Liposomal encapsulation masks genotoxicity of a chemotherapeutic agent in regulatory toxicology assessments

Alexander, Jenolyn F.; Aguirre-Villarreal, David; Godin, Biana

doi:10.1016/j.nano.2016.12.016

Cited by 11 publications

(6 citation statements)

References 18 publications

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“…The direct mutagenicity of nanoformulations in Salmonella typhimurium auxotrophs for the histidine operon, strains TA98, TA100, TA1535, TA1537 and TA102, were determined, in triplicate, using the maximum tolerated doses and four consecutive dilutions to the third according to the Organization for Economic Cooperation and Development (OECD) recommendations [ 43 ]. The average of the number of mutated colonies was graphed in function of the concentration and the mutagenic powers (MPs, slope of the initial linear portion) were extracted for each tested strain [ 44 , 45 , 46 , 47 ].…”

Section: Methodsmentioning

confidence: 99%

Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

et al. 2021

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2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM), Fourier transform infrared analysis and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to seven times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (up to 70%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (−1.59 to −26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).

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Section: Methodsmentioning

confidence: 99%

Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

et al. 2021

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“…Therefore, the pre-existing knowledge has provided the basis for this study hypothesis since liposomes are regarded as biocompatible and non-genotoxic [ 42 , 43 ]; nonetheless, literature suggests that they have the potential to mask the toxic effects of some encapsulated materials [ 44 ]. Data relating to the genotoxicity of polyacryl-cyanoacrylate (PACA) nanoparticles is also extremely scarce despite being this material an emerging material for advanced drug carrier.…”

Section: Introductionmentioning

confidence: 99%

Evaluating nanobiomaterial-induced DNA strand breaks using the alkaline comet assay

Tutty

Vella

Vennemann³

et al. 2022

Drug Deliv. and Transl. Res.

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Due to their unique chemical and physical properties, nanobiomaterials (NBMs) are extensively studied for applications in medicine and drug delivery. Despite these exciting properties, their small sizes also make them susceptible to toxicity. Whilst nanomaterial immunotoxicity and cytotoxicity are studied in great depth, there is still limited data on their potential genotoxicity or ability to cause DNA damage. In the past years, new medical device regulations, which came into place in 2020, were developed, which require the assessment of long-term NBM exposure; therefore, in recent years, increased attention is being paid to genotoxicity screening of these materials. In this article, and through an interlaboratory comparison (ILC) study conducted within the Horizon 2020 REFINE project, we assess five different NBM formulations, each with different uses, namely, a bio-persistent gold nanoparticle (AuNP), an IR-780 dye-loaded liposome which is used in deep tissue imaging (LipImage™815), an unloaded PACA polymeric nanoparticle used as a drug delivery system (PACA), and two loaded PACA NBMs, i.e. the cabazitaxel drug-loaded PACA (CBZ-PACA) and the NR668 dye-loaded PACA (NR668 PACA) for their potential to cause DNA strand breaks using the alkaline comet assay and discuss the current state of genotoxicity testing for nanomaterials. We have found through our interlaboratory comparison that the alkaline comet assay can be suitably applied to the pre-clinical assessment of NBMs, as a reproducible and repeatable methodology for assessing NBM-induced DNA damage. Graphical abstract Workflow for assessing the applicability of the alkaline comet assay to determine nanobiomaterial (NBM)-induced DNA strand breaks, through an interlaboratory comparison study (ILC)

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“…Huge effort has been placed in recent years on designing NBMs that can increase drug delivery, be more sensitive and more speci c for imaging. Poly(alkyl cyanoacrylate), or PACA NBMs, which were rst developed and approved as surgical glues, have proven in recent years to be promising drug carriers because of not only their high loading capacity but also their biodegradability [64,65] Liposomes are generally regarded as non-toxic and biocompatible, and it has been shown that they do in fact mask some of the genotoxic potential of the drug or materials they encapsulate [40]. When incubated with the IR-780 liposome LipImage, HepG2 cells show no DNA damage notable (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the pre-existing knowledge (i.e., read-across) available in literature provided the basis for this study hypothesis since liposomes are regarded as biocompatible and non-genotoxic [38,39], nonetheless literature suggests that they have the potential to mask the toxic effects of some encapsulated materials [40]. Data relating to the genotoxicity of polyacryl-cyanoacrylate (PACA) nanoparticles is also extremely scarce despite being this material an emerging material for advanced drug carrier.…”

Section: Introductionmentioning

confidence: 99%

Evaluating Nanobiomaterial induced DNA strand breaks using the alkaline Comet Assay

Tutty

Vella

Prina‐Mello

et al. 2022

Preprint

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Due to their unique chemical and physical properties, nanobiomaterials (NBM’s) are extensively studied for applications in medicine and drug delivery. Despite these exciting properties, their small sizes also make them susceptible to toxicity. Whilst nanomaterial immunotoxicity and cytotoxicity are studied in great depth, there is still limited data on their potential genotoxicity, or their potential to cause DNA damage. In the past two years new medical device regulations, which come into place in 2020, have been developed. These require the assessment of long-term NBMs exposure, and also drug delivery systems and nanomedicines, therefore in recent years increased attention is being paid to genotoxicity screening of these materials. In this article, we assess three different particle formulations which different uses, a bio-persistent gold nanoparticle (AuNP), an IR-780 dye loaded liposome which is used in deep tissue imaging, an unloaded PACA polymeric nanoparticle used as a drug delivery system, and two loaded PACA NBMs (CBZ and NR668) for their potential to cause DNA strand breaks using the alkaline Comet Assay and discuss the current state of genotoxicity testing for nanomaterials.

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Liposomal encapsulation masks genotoxicity of a chemotherapeutic agent in regulatory toxicology assessments

Cited by 11 publications

References 18 publications

Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

Evaluating nanobiomaterial-induced DNA strand breaks using the alkaline comet assay

Evaluating Nanobiomaterial induced DNA strand breaks using the alkaline Comet Assay

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