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Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells

1
Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy
2
Department of Experimental Medicine (DIMES), University of Genova, Via Alberti L.B., 16132 Genoa, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Antioxidants 2020, 9(1), 50; https://doi.org/10.3390/antiox9010050
Received: 28 November 2019 / Revised: 24 December 2019 / Accepted: 31 December 2019 / Published: 6 January 2020
Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX 5) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (−45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX 5 was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX 5 is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells. View Full-Text
Keywords: etoposide; lab-made biodegradable dendrimer; nanoparticle formulation; improved solubility; neuroblastoma cells; synergistic action; protracted release etoposide; lab-made biodegradable dendrimer; nanoparticle formulation; improved solubility; neuroblastoma cells; synergistic action; protracted release
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Alfei, S.; Marengo, B.; Domenicotti, C. Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells. Antioxidants 2020, 9, 50.

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