1. Translation of nanomedicines from lab to industrial scale synthesis: The case of squalene-adenosine nanoparticles
- Author
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Marie Rouquette, Arnaud Peramo, Clement Mahatsekake, Romain Brusini, Mariana Varna, Sinda Lepetre-Mouelhi, Flavio Dormont, Didier Desmaële, Serge Calet, Frédéric Gobeaux, Patrick Couvreur, Fabienne Testard, Institut Galien Paris-Sud (IGPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), HOLOCHEM, Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire (LIONS), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Fondation pour la Recherche Médicale (FRM) grant number ECO20160736101, ANR-16-ENM2–0005-01,NanoHeart,NanoHeart, Institut Galien Paris-Saclay (IGPS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Rayonnement Matière de Saclay (IRAMIS), ANR-16-ENM2-0005,NanoHeart,Squalene-Adenosine nanoparticles for heart ischemia/reperfusion injuries treatment(2016), Institut de Biologie et de Technologies de Saclay (IBITECS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Physico-chimie, pharmacotechnie, biopharmacie (PCPB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS)
- Subjects
Multiple stages ,Male ,Squalene ,Adenosine ,Cell Survival ,Pharmaceutical Science ,Nanoparticle ,Nanotechnology ,Context (language use) ,impurity profile ,02 engineering and technology ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,Cell Line ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Animals ,scaling-up nanomedicines ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,Chemistry ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Industrial scale ,[CHIM.MATE]Chemical Sciences/Material chemistry ,Blood Proteins ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,021001 nanoscience & nanotechnology ,Biocompatible material ,drug development ,[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology ,Nanomedicine ,Drug development ,Nanoparticles ,Adsorption ,Nanocarriers ,0210 nano-technology - Abstract
International audience; A large variety of nanoparticle-based delivery systems have become increasingly important for diagnostic and/or therapeutic applications. Yet, the numerous physical and chemical parameters that influence both the biological and colloidal properties of nanoparticles remain poorly understood. This complicates the ability to reliably produce and deliver well-defined nanocarriers which often leads to inconsistencies, conflicts in the published literature and, ultimately, poor translation to the clinics. A critical issue lies in the challenge of scaling-up nanomaterial synthesis and formulation from the lab to industrial scale while maintaining control over their diverse properties. Studying these phenomena early on in the development of a therapeutic agent often requires partnerships between the public and private sectors which are hard to establish. In this study, through the particular case of squalene-adenosine nanoparticles, we reported on the challenges encountered in the process of scaling-up nanomedicines synthesis. Here, squalene (the carrier) was functiona-lized and conjugated to adenosine (the active drug moiety) at an industrial scale in order to obtain large quantities of biocompatible and biodegradable nanoparticles. After assessing nanoparticle batch-to-batch consistency , we demonstrated that the presence of squalene analogs resulting from industrial scale-up may influence several features such as size, surface charge, protein adsorption, cytotoxicity and crystal structure. These analogs were isolated, characterized by multiple stage mass spectrometry, and their influence on nanoparticle properties further evaluated. We showed that slight variations in the chemical profile of the nanocarrier's constitutive material can have a tremendous impact on the reproducibility of nanoparticle properties. In a context where several generics of approved nanoformulated drugs are set to enter the market in the coming years, characterizing and solving these issues is an important step in the pharmaceutical development of nanomedicines.
- Published
- 2019
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