Nanotoxicological and teratogenic effects: A linkage between dendrimer surface charge and zebrafish developmental stages

Calienni, Maria; Feas, Daniela Agustina; Igartúa, Daniela E.; Chiaramoni, Nadia Silvia; Prieto, María Jimena

doi:10.1016/j.taap.2017.10.003

Cited by 30 publications

(11 citation statements)

References 57 publications

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“…In non-lethal doses, complexes did not cause any other effects. Results are consistent with those obtained by Calienni et al (2017), in which free DG4.0 were lethal for zebrafish larvae in concentrations higher than 0.5 µM . Taking into account these results to those previously obtained ex vivo and in vitro, we can conclude that the DG4.5-CBZ complexes were non-toxic and biocompatible in the concentrations tested.…”

Section: In Vivo Biocompatibility: Zebrafish Larvaesupporting

confidence: 91%

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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Carbamazepine (CBZ) is an antiepileptic drug, which also could be used in the treatment of neurodegenerative diseases, such as the Alzheimer's disease. However, its use has been limited due to its low solubility, inefficient pharmacokinetic profiles, and multiple side effects. PAMAM dendrimers, ethylenediamine core, generation 4.0 (amine terminal groups) and 4.5 (carboxylate terminal groups) (DG4.0 and DG4.5 respectively) are polymers that can increase drug solubility through complexation. Thus, the aim of this work was to obtain and characterize complexes between CBZ and dendrimers. Both DG4.0 and DG4.5 allowed the incorporation of ∼20 molecules of CBZ per dendrimer, into their hydrophobic pockets. DG4.0-CBZ and DG4.5-CBZ complexes were found to be stable for 90 days at 37 °C and resistant to a lyophilization process, presenting controlled drug release. Also, the complexes nanotoxicity was tested ex vivo (human red blood cells), in vitro (N2a cell line), and in vivo (zebrafish). No hemolytic effect was observed in the ex vivo model. As regards in vitro toxicity, the DG4.5-CBZ complexes significantly reduced the toxicity caused by the free drug. Moreover, the DG4.5-CBZ did not cause neurotoxicity or cardiotoxicity in zebrafish larvae. In conclusion, a stable and biocompatible drug delivery system based on the DG4.5 capable of complex the CBZ has been developed. This achievement highlights the advantages of using negatively charged dendrimers for nanomedicine.

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Section: In Vivo Biocompatibility: Zebrafish Larvaesupporting

confidence: 91%

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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“…Activity events were recorded for 15 min at 4, 24, 48, and 72 h post-incubation (hpi) at room temperature with an automated device with a system of infrared detection (WMicrotracker, Designplus SRL, Buenos Aires, Argentina) [32]. Swimming activity was determined as the number of interruptions of the infrared microbeam arrangement for 15 min and data were relativized to the control [33]. A total of eight wells per condition were analyzed by triplicate.…”

Section: Measurement Of the Swimming Activitymentioning

confidence: 99%

“…High or low activity with respect to the control could be indicative of adverse effects on one or more components of the complex neuronal network that governs the early locomotor system (spinal cord and hindbrain) [63]. Because in vertebrates, serotonin plays a key role in the modulation of locomotor movements [64], further studies of changes in the raphe populations of zebrafish brain could give additional evidence of the neurotoxicity of the treatment [33,65].…”

Section: In Vivo Toxicity Evaluationmentioning

confidence: 99%

Nano-formulation for topical treatment of precancerous lesions: skin penetration, in vitro, and in vivo toxicological evaluation

Calienni

Temprana

Prieto

et al. 2017

Drug Deliv. and Transl. Res.

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With the aim of improving the topical delivery of the antineoplastic drug 5-fluorouracil (5FU), it was loaded into ultradeformable liposomes composed of soy phosphatidylcholine and sodium cholate (UDL-5FU). The liposome populations had a mean size of 70 nm without significant changes in 56 days, and the ultradeformable formulations were up to 324-fold more elastic than conventional liposomes. The interaction between 5FU and the liposomal membrane was studied by three methods, and also release profile was obtained. UDL-5FU did penetrate the stratum corneum of human skin. At in vitro experiments, the formulation was more toxic on a human melanoma-derived than on a human keratinocyte-derived cell line. Cells captured liposomes by metabolically active processes. In vivo toxicity experiments were carried out in zebrafish (Danio rerio) larvae by studying the swimming activity, morphological changes, and alterations in the heart rate after incubation. UDL-5FU was more toxic than free 5FU. Therefore, this nano-formulation could be useful for topical application in deep skin precancerous lesions with advantages over current treatments. This is the first work that assessed the induction of apoptosis, skin penetration in a Saarbrücken penetration model, and the toxicological effects in vivo of an ultradeformable 5FU-loaded formulation.

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“…Second, teratogenicity is evaluated based on abnormal eye development, lack of spontaneous movement, unusual heart rate, lack of pigmentation, and edema. The standard shows normal development [ 60 , 127 ].…”

Section: Using Zebrafish Embryos To Detect Developmental Toxicitymentioning

confidence: 99%

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

Chahardehi

Arsad

Lim

2020

Plants

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The zebrafish (Danio rerio) is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. The zebrafish embryotoxicity model is at the leading edge of toxicology research due to the short time required for analyses, transparency of embryos, short life cycle, high fertility, and genetic data similarity. Zebrafish toxicity studies range from assessing the toxicity of bioactive compounds or crude extracts from plants to determining the optimal process. Most of the studied extracts were polar, such as ethanol, methanol, and aqueous solutions, which were used to detect the toxicity and bioactivity. This review examines the latest research using zebrafish as a study model and highlights its power as a tool for detecting toxicity of medicinal plants and its effectiveness at enhancing the understanding of new drug generation. The goal of this review was to develop a link to ethnopharmacological zebrafish studies that can be used by other researchers to conduct future research.

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Nanotoxicological and teratogenic effects: A linkage between dendrimer surface charge and zebrafish developmental stages

Cited by 30 publications

References 57 publications

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Nano-formulation for topical treatment of precancerous lesions: skin penetration, in vitro, and in vivo toxicological evaluation

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

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