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A New Lipid-Based Nano Formulation of Vinorelbine

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Abstract

Vinorelbine (VLB) is a semi-synthetic Vinca alkaloid which is currently used in treatment of different cancer types mainly advanced breast cancer (ABC) and advanced/metastatic non-small cell lung cancer (NSCLC). However, its marketed formulation has been reported to have serious side effects, such as granulocytopenia, which is the major dose-limiting toxicity. Other unwanted effects include venous discoloration and phlebitis proximal to the site of injection, as well as localized rashes and urticaria, blistering, and skin sloughing. Our long-term aim in synthesizing a novel nanomicellar vinorelbine formulation is to reduce or even eliminate these side effects and increase drug activity by formulating the drug in a lipid-based system as a nanomedicine targeted to the site of action. To this end, the purpose of this study was to prepare, characterize, and determine the in vitro efficacy of vinorelbine-loaded sterically stabilized, biocompatible, and biodegradable phospholipid nanomicelles (SSM; size, ∼15 nm). Our results indicated that vinorelbine incorporate at high quantities and within the interface between the core and palisade sections of the micelles. Incorporation ratio of drug within sterically stabilized micelles increased as the total amount of drug in the system increased, and no drug particles were formed at the highest drug concentrations tested. The nanomicellar formulation of vinorelbine was ∼6.7-fold more potent than vinorelbine dissolved in DMSO on MCF-7 cell line. Collectively, these data indicate that vinorelbine-loaded SSM can be developed as a new, safe, stable, and effective nanomedicine for the treatment of breast and lung cancers.

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ACKNOWLEDGMENTS

This study was supported, in part, by NIH grant CA121797. Most part of this investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number CO6RR15482 from the National Center for Research Resources, NIH. Also, the authors would like to thank Dr. Antonina Kuzmis for her very precious advices and assistance during the experimentations.

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Authors and Affiliations

  1. Department of Biopharmaceutical Sciences (M/C 865), College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, 60612-7231, USA

    Fatemeh Bahadori & Hayat Önyüksel

  2. Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University, 34469, Maslak, Istanbul, Turkey

    Fatemeh Bahadori & Gülaçtı Topçu

  3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Bezmialem Vakif University, 34093, Fatih, Istanbul, Turkey

    Fatemeh Bahadori & Gülaçtı Topçu

  4. Engineering Faculty, Department of Chemical Engineering, Marmara University, 34722, Kadikoy, Istanbul, Turkey

    Mehmet S. Eroğlu

  5. Chemistry Group Laboratories, TUBITAK-UME, PO Box 54, 41471, Gebze, Kocaeli, Turkey

    Mehmet S. Eroğlu

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  1. Fatemeh Bahadori
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  2. Gülaçtı Topçu
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  3. Mehmet S. Eroğlu
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  4. Hayat Önyüksel
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Correspondence to Hayat Önyüksel.

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Bahadori, F., Topçu, G., Eroğlu, M.S. et al. A New Lipid-Based Nano Formulation of Vinorelbine. AAPS PharmSciTech 15, 1138–1148 (2014). https://doi.org/10.1208/s12249-014-0146-3

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  • DOI: https://doi.org/10.1208/s12249-014-0146-3

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