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Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent

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Abstract

Purpose

The objective was to develop, characterize and assess the potentiality of W1/O/W2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI).

Methods

For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions.

Results

Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference.

Conclusion

New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

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Abbreviations

DLS:

Dynamic Light Scattering

DSC:

Differential Scanning Calorimetry

DTPA-Eu:

Diethylene tri-amine penta acetic acid—Europium

DTPA-Gd:

Diethylene tri-amine penta acetic acid—Gadolinium

E.E:

Encapsulation efficiency

HSA:

Human Serum Albumin

ICP-AES:

Inductively Coupled Plasma Absorption Emission Spectroscopy

ICP-MS:

Inductively Coupled Plasma Mass Spectrometry

MDS:

Mean Droplet Size

MRI:

Magnetic Resonance Imaging

PDI:

Polydispersity Index

TEM:

Transmission Electron Microscopy

TGA:

Thermo Gravimetric Analysis

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors wish to thank Jean-Michel Guigner, Institut de minéralogie et de physique des milieu condensés IMPC-IRD-CNRS UMR 7590, UPMC for his support for TEM imaging and ED387-iViV, UPMC Sorbonne Université, Paris, France for supporting this project.

We thank the Maison des Langues, Université Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris France for their review of the English manuscript.

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Authors and Affiliations

  1. U1022 INSERM, UMR8258 CNRS, Unité de Technologies Chimiques et Biologiques pour la Santé, Chimie ParisTech, Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cité, 75006, Paris, France

    Estelle Sigward, Yohann Corvis, Bich-Thuy Doan, Kadri Kindsiko, Johanne Seguin, Daniel Scherman, Denis Brossard, Nathalie Mignet, Philippe Espeau & Sylvie Crauste-Manciet

  2. ARNA Laboratory, ChemBioMed U869, Pharmaceutical Science Faculty, University of Bordeaux, 146 rue Leo Saignat, 33000, Bordeaux, France

    Sylvie Crauste-Manciet

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  1. Estelle Sigward
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  2. Yohann Corvis
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Correspondence to Sylvie Crauste-Manciet.

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Sigward, E., Corvis, Y., Doan, BT. et al. Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent. Pharm Res 32, 2983–2994 (2015). https://doi.org/10.1007/s11095-015-1680-8

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  • DOI: https://doi.org/10.1007/s11095-015-1680-8

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