Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice.

Nathalie Wauthoz, Guillaume Bastiat, Elodie Moysan, Anna Cieślak, Kazuya Kondo, Marc Zandecki, Valérie Moal, Marie-Christine Rousselet, José Hureaux, Jean-Pierre Benoit

Index: Nanomedicine: Nanotechnology, Biology, and Medicine 11 , 1237-45, (2015)

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Abstract

The purpose of this study is the assessment of gel technology based on a lauroyl derivative of gemcitabine encapsulated in lipid nanocapsules delivered subcutaneously or intravenously after dilution to (i) target lymph nodes, (ii) induce less systemic toxicity and (iii) combat mediastinal metastases from an orthotopic model of human, squamous, non-small-cell lung cancer Ma44-3 cells implanted in severe combined immunodeficiency mice. The gel technology mainly targeted lymph nodes as revealed by the biodistribution study. Moreover, the gel technology induced no significant myelosuppression (platelet count) in comparison with the control saline group, unlike the conventional intravenous gemcitabine hydrochloride treated group (P<0.05). Besides, the gel technology, delivered subcutaneously twice a week, was able to combat locally mediastinal metastases from the orthotopic lung tumor and to significantly delay death (P<0.05) as was the diluted gel technology delivered intravenously three times a week.Lung cancer is one of the leading causes of mortality worldwide. A significant proportion of patients with this disease have lymph node metastasis. In this study, the authors investigated the use of lipid nanocapsules, loaded with the lipophilic pro-drug gemcitabine for targeting tumors in lymph nodes after subcutaneous injection. This delivery method was shown to be effective in controlling tumor progression and may be useful in future clinical use.Copyright © 2015 Elsevier Inc. All rights reserved.