Original Article
In vitro anti-cancer effects of artemisone nano-vesicular formulations on melanoma cells

https://doi.org/10.1016/j.nano.2015.07.010Get rights and content

Abstract

Artemisone is a 10-amino-artemisinin derivative that is markedly superior in vitro and in vivo to current artemisinins against malaria and also possesses antitumor activity. In seeking to capitalise on the last property, we have examined the encapsulation of artemisone in nano-vesicular niosomes and solid lipid nanoparticles, and have evaluated efficacies of the free and encapsulated artemisone against human melanoma A-375 cells and effects on human keratinocytes (HaCaT). Artemisone is successfully encapsulated into the nano-vesicles with encapsulation efficiencies of 67 ± 6% and 79 ± 5%, and with average particle sizes being 211 ± 10 nm and 295 ± 18 nm respectively. The formulations displayed highly selective cytotoxicity towards the melanoma cells with negligible toxicity towards the normal skin cells. The artemisone-loaded nano-vesicles almost completely inhibited the melanoma cells compared to the free drug. The results overall suggest a potentially more useful therapeutic strategy that needs to be evaluated for the treatment of melanoma and other cancers.

From the Clinical Editor

Apart from being an effective anti-malarial drug, a surprising action of artemisone also has antitumor activity. Nonetheless, its low water solubility and bioavailability has limited its clinical use. In this article, the authors enacapsulated artemisone in nano- vesicles and solid lipid nano-particles (SLNs). In-vitro studies confirmed the selective cytotoxicity towards melanoma cells. Further in-vivo and pre-clinical studies are awaited.

Graphical Abstract

Artemisone, a new artemisinin derivative, was encapsulated in nano-vesicular niosome and solid lipid nanoparticles with the aim of enhancing its efficacy against melanoma cells. The formulated artemisone displayed highly selective and significant cytotoxicity when compared to free artemisone. The toxicity of these formulations was also evaluated on human keratinocytes; no significant effects were observed, thus indicating a substantial safety profile. Importantly, these formulations also ameliorated the effects of artemisone on human keratinocytes when compared to free artemisone. The results overall suggest a potent therapeutic strategy that needs to be evaluated for the treatment of melanoma and other cancers.

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Section snippets

Methods

Full details of materials and methods appear in the supplementary material.

Particle size and zeta potential of niosomes and SLNs

Since adequate characterisation of these nano-vesicles is crucial for ensuring reproducibility of the results, particle size, zeta potential, structure morphology, encapsulation efficiency of the niosomes and SLNs were carefully evaluated. The size ranges (nm), zeta potentials (mV) and encapsulation efficiencies (EE%) obtained are listed in Table 1. For preparation of the niosomes, the effect of the sorbitan monostearate:cholesterol ratio on the stability and size of the niosomes was evaluated.

Discussion

This study was aimed at evaluating the anticancer effects of artemisone and its nano-vesicular formulation on human melanoma cells with normal human keratinocytes being used as a control. Artemisone was entrapped into two different types of nano-vesicles – niosomes and SLNs. It was anticipated that due to their nanoscale structure, these carriers would efficiently penetrate the cells and enhance drug efficacy according to literature precedent involving other drugs.19, 20, 21, 22 One previous

Acknowledgements

We would like to thank Laura Guembe (Servicio de Morfología, Centro para la Investigación Médica Aplicada, CIMA), Ainhoa Urbiola and Cristina Ederra (Unidad de Imagen, CIMA) for their excellent technical support with imaging techniques.

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    Source of funding: This work was carried out with the financial support of the National Research Foundation of South Africa (NRF) (grants no. IFRR81178 and CPRR13091742482), the MAL-TB REDOX MRC Flagship Project and the Centre of Excellence for Pharmaceutical Sciences (Pharmacen) of the North-West University, Potchefstroom Campus, South Africa.

    Disclaimer: Any opinions, findings and conclusions, or recommendations expressed in this material are those of the authors and therefore the NRF does not accept any liability in regard thereto.

    Conflict of Interest: None of the authors have any conflict of interest to declare.

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