Research Article

Preparation and evaluation of etoposide-loaded lipid-based nanosuspensions for high-dose treatment of lymphoma

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China

‡Authors contributed equally

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Leiqiang Han^‡

‡Authors contributed equally

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Shengjun Mu

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Weiwei Mu

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Shuang Liang

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Tianqi Wang

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Yongjun Liu

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Na Zhang

*Author for correspondence: Tel.: +86 0531 8838 2015; Fax: +86 0531 8838 2548;

E-mail Address: zhangnancy9@sdu.edu.cn

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Published Online:10 Jun 2019https://doi.org/10.2217/nnm-2018-0502

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Abstract

Aim: High-dose administration of etoposide (VP16) was limited by its poor aqueous solubility and severe systemic toxicity on lymphoma therapy. Herein, a novel VP16-loaded lipid-based nanosuspensions (VP16-LNS) was developed for improving drug solubility, enhancing antitumor effect and reducing systemic toxicity. Materials & methods: VP16-LNS with soya lecithin and D-α-tocopheryl PEG 1000 succinate (TPGS) as stabilizers were prepared by nanoprecipitation method. Results: VP16-LNS exhibited uniform spherical morphology, small particle size and favorable colloidal stability. The concentration of VP16 in VP16-LNS was high enough (1017.67 μg/ml) for high-dose therapy on lymphoma. Moreover, VP16-LNS displayed long blood circulation time, selective intratumoral accumulation, remarkable antitumor effect and upregulated safety. Conclusion: VP16-LNS would be an efficient nanoformulation for clinical intravenous application against lymphoma.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 14, No. 11

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History

Received 18 December 2018

Accepted 26 February 2019

Published online 10 June 2019

Published in print June 2019

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/full/10.2217/nnm-2018-0502

Financial & competing interests disclosure

This work was supported by a grant from the National Natural Science Foundation of China (No. 81773652, No. 81573368); and the Young Scholar Program of Shandong University (YSPSDU, 2017WLJH40). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The animal experiments were conducted with the approval of the Laboratory Animal Ethical and Welfare Committee of Shandong University Cheeloo College of Medicine. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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