Special Issue on Aptamers in Drug Delivery

November 16, 2018 - We have edited a special issue of Advanced Drug Delivery Reviews entitled "Aptamers in Drug Delivery". As we have been working for several years on the design and use of aptamers for guiding liposomes to therapeutic target, with the contribution of several world experts in the field, we have managed to produce a sum of articles that cover a wide variety of topics ranging from chemistry to therapeutic applications through including our review "Aptamer-guided nanomedicines for anticancer drug delivery ". Learn more

Commercialisation d’un traitement d'urgence contre les actinides : l’aboutissement de 10 années de recherche du LRSI et de mon équipe

http://www.umr-cnrs8612.u-psud.fr/images/cevidra.jpgL’entreprise Cevidra commercialise depuis le mois de juillet 2018 Cevidra® Calixarene, le premier traitement local d’urgence pour une contamination cutanée par un actinide (uranium, plutonium, américium, etc.). Ce traitement, une crème lavante très simple d’utilisation, qui empêche l’uranium de passer la barrière de la peau à plus de 95 % si elle est appliquée immédiatement, a été mis au point au cours de deux thèses dans le laboratoire de recherche en radiochimie, spéciation et imagerie (LRSI)  de l’IRSN en partenariat avec l’Institut Galien Paris Sud (UMR CNRS 8612) et la Direction Générale de l’Armement (DGA). Présentée en avant-première sur le salon World Nuclear Exhibition de Paris (26-28 juin 2018), événement international du nucléaire, cette crème a valu à l'entreprise Cevidra de décrocher l'Award WNE "sûreté nucléaire" dans la catégorie TPE-PME. 

Le brevetCevidra - Article sur le site de l'IRSN

Article: Elucidating the role of surface chemistry on cationic phosphorus dendrimer–siRNA complexation

tsapisJune 12, 2018 - This paper is a joint collboration with the Istituto Dalle Molle di studi sull'Intelligenza Artificiale (IDSIA) in Lugano (Switzerlan) and the Laboratoire de Chimie de Coordination, in Toulouse. In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the flexibility/rigidity ratio, play a crucial role in the efficiency of complexation. However, advances in organic chemistry have enabled the development of dendrimers that differ only by a single atom on their surface terminals. This is the case for cationic phosphorus dendrimers functionalized with either pyrrolidinium (DP) or morpholinium (DM) terminal groups. This small change was shown to strongly affect the dendrimer–siRNA complexation, leading to more efficient anti-inflammatory effects in the case of DP. Reasons for this different behavior can hardly be inferred only by biological in vitro and in vivo experiments due to the high number of variables and complexity of the investigated biological system. However, an understanding of how small chemical surface changes may completely modify the overall dendrimer–siRNA complexation is a significant breakthrough towards the design of efficient dendrimers for nucleic acid delivery. Herein, we present experimental and computational approaches based on isothermal titration calorimetry and molecular dynamics simulations to elucidate the molecular reasons behind different efficiencies and activities of DP and DM. Results of the present research highlight how chemical surface modifications may drive the overall dendrimer–siRNA affinity by influencing enthalpic and entropic contributions of binding free energy. Moreover, this study elucidates molecular reasons related to complexation stoichiometry that may be crucial in determining the dendrimer complexation efficiency.

15 February 2018 - Wtih Stavros Kassinos from the University of Cyprus, we have edited in European Journal of Pharmceutical Sciences a special issue dedicated to COST Action SimInhale: cross-disciplinary perspective on the current state of the art and challenges in pulmonary drug delivery

Award: The Maurice-Marie Janot Award 2018

I have been selected by an international scientific committee of 70 scientific personalities as the Maurice-Marie Janot Award 2018. The first edition of this prize goes back to 1986. It is given by the European association APGI and sponsored by the company Sanofi. I will receive the award at the 11th World Meeting on Pharmaceuticals, Biopharmaceutics and Pharmaceutical Technology to be held in Granada (Spain) from March 19 to 22, 2018. This congress brings together around 1500 participants making it the world's first congress in the field of drug delivery. On this occasion, I will give a plenary lecture entitled "Tackling physiological resistances to drug delivery". (list of  previsous awardees).

Article: Aptamer-guided siRNA-loaded nanomedicines for systemic gene silencing in CD-44 expressing murine triple-negative breast cancer model

In this study, we describe a liposome-based siRNA delivery system with a core composed of siRNA:protamine complex and a shell designed for the active targeting of CD44-expressing cells using for the first time the anti-CD44 aptamer (named Apt1) as targeting ligand. Among all functions, CD44 is the most common cancer stem cell surface biomarker and is found overexpressed in many tumors making this an attractive receptor for therapeutic targeting. This unique non-cationic system was evaluated for the silencing of the reporter gene of luciferase (luc2) in a triple-negative breast cancer model in vitro and in vivo. We show the possibility of conjugating an aptamer to siRNA-containing liposomes for an efficient gene silencing in CD44-expressing tumor cells in vivo, in the perspective of silencing disease-related genes in tumors.

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