Biodistribution of polycyanoacrylate nanoparticles encapsulating doxorubicin by Matrix-Assisted Laser Desorption Ionization (MALDI) Mass Spectrometry Imaging (MSI)

Christelle Zandanel (1), Raphael Legouffe (2,3), Veronique Trochon-Joseph (1), Aurore Tomezyk (2,3), Mathieu Gaudin (2,3), David Bonnel (2,3), Jonathan Stauber (2,3), Bérangère Vasseur (1), Norbert Bromet (4)

1) Onxeo, 49 bd Génénal Martial Valin, 75015, Paris, France
2) ImaBiotech, Parc Eurasanté, 152 rue du Docteur Alexandre Yersin, 59120, Loos France
3) ImaBiotech Corp, 44 Manning Rd, Billerica, MA, 01821, United States
4) External Consultant, 127 rue de la Verronnerie, Dry, 45370, France
Journal of Drug Delivery Science and Technology, Volume 47, October 2018

Abstract
Nanoparticles are widely used as carrier for the delivery of Active Principle Ingredients (API). From safety point of view, the fate of nanoparticles and API after administration becomes a key question. Today qualitative and quantitative biodistribution of such carriers or encapsulated API can be performed by chemical modification with a fluorescent probe or a radiolabeling and require a first acquisition step for visualization and a second step for quantification by tissues extraction. LC-MS/MS can be considered but the information about the localization of the API is lost.

After a long period focused on the sample preparation method development, Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) is nowadays recognized as the most promising technique for the study of biodistribution of small molecular weight API without additional labeling, combining a visual and quantitative approach.

In this study, we extended the scope of use of MALDI-MSI to polycyanoacrylate nanoparticles loaded with doxorubicin. MALDI-MSI allowed the detection and quantification of doxorubicin and polycyanoacrylate, the polymer used as carrier, forming the nanoparticles in mouse liver section. Additionally, MALDI-MSI was able to detect doxorubicinol, the metabolite of doxorubicin.

This Proof Of Concept was successful emphasizing the benefits of this technique (label free and quantitative approach) and offers the possibility to use a unique technique for the detection of encapsulated API and the carrier opening a wide field of application in drug delivery of formulated API.

Keywords
Nanoparticles; Doxorubicin; Matrix-Assisted Laser Desorption Ionization (MALDI); Mass Spectrometry Imaging (MSI)

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