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. 2014 Oct;15(5):1138-48.
doi: 10.1208/s12249-014-0146-3. Epub 2014 May 29.

A new lipid-based nano formulation of vinorelbine

Fatemeh Bahadori  1 , Gülaçtı Topçu, Mehmet S Eroğlu, Hayat Onyüksel
Affiliations

A new lipid-based nano formulation of vinorelbine

Fatemeh Bahadori et al. AAPS PharmSciTech. 2014 Oct.

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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Figures

Fig. 1
Fig. 1
The structure of vinorelbine
Fig. 2
Fig. 2
NICOMP size distribution analysis of 500µg VLB in 1 mM SSM, (INT-WT (left) VOL-WT (right))
Fig. 3
Fig. 3
% VLB associated with 1mM DSPE-PEG followed by centrifuge assay
Fig. 4
Fig. 4
VLB (5 mg) association with DSPE-PEG (10mM) before and after lyophilization
Fig. 5
Fig. 5
Release of VLB from SSM by dialysis
Fig. 6
Fig. 6
Characterization of VLB-SSM Formulation Using (DSC), (a): DSC thermogram of solid DSPE-PEG 2000 (commercially obtained powder), (b): DSC Thermogram of solid DSPE-PEG 2000 after making SSM, (c): Thermogram of 500µg VLB associated with SSM after lyophilization, (d): The thermogram of solid Vinorelbine
Fig. 7
Fig. 7
VLB Activity on MCF-7 Cells in 72 h as free drug or in SSM
Fig. 8
Fig. 8
IC50 values of VLB loaded SSM and Free VLB
Fig. 9
Fig. 9
Cytotoxic activity of controls
Fig. 10
Fig. 10
Localization of VLB in between 2 DSPE-PEG unimers and observation of a decrease in size of particle
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