Speaker at Global conference on Pharmaceutics and Drug Delivery Systems 2019 - Amanda Silva Brun
Universite Paris Diderot, France
Title : Designing extracellular vesicles for bio-camouflaged drug delivery and cell-free regenerative medicine


Extracellular vesicles (EVs) are multifaceted subcellular entities that may represent a new generation of bio-camouflaged drug/ nanoparticle delivery system and regenerative medicine effectors. In a top-down procedure, our group has engineered nanoparticle/drug-loaded EVs from precursor cells previously loaded with this cargo. EVs from HUVEC cells and THP1 macrophages were tested for anti-tumor therapy. Concerning regenerative medicine, EVs were obtained from adipose stem cells and tested in a fistula model.  By using our method, EVs could encapsulate a set of nanoparticles regardless their chemistry or shape. These hybrid vesicles were able to generate heat when submitted to an alternating magnetic field and could be monitored by fluorescence imaging or MRI. Dual drug/nanoparticle EV loading was also feasible by this method. We demonstrated that vesicles from THP-1 cells could be loaded with iron oxide nanoparticles and different therapeutic agents irrespective to their molecular weight, hydrophobic, hydrophilic and amphiphilic character. The theranostic potential of mTHPC-loaded magnetic EVs was tested in vivo in a murine tumoral model. Vesicles could be tracked in vivo by dual-mode imaging, combining optical imaging and MRI. The engineered EVs were found to induce an efficient photodynamic action, as evidenced by tumor growth curves and histological analysis. The regenerative properties of EVs obtained from adipose stem cells was demonstrated in a fistula model. In brief, we succeeded in customizing EV by engineering them to display several nanoparticle/drug cargoes featuring therapeutic and imaging properties both in vitro and in vivo. EV regenerative effect was for the first time demonstrated for fistula therapy.
Audience take away: 
• How we can convert biological messengers into a bio-camouflaged delivery system
• Production and engineering methods to do so.
• In vitro and in vivo properties of the designed extracellular vesicles.


Amanda Silva obtained a degree in Pharmacy in 2005 and a PhD in Pharmaceutical Technology in 2008 both from UFRN, Natal, Brazil and a second PhD in Cellular and Molecular Biology in 2010 concerning polysaccharides for thermo-controlled cell culture at Université d’Evry/Université Paris V. She worked as a postdoctoral fellow on drug-loaded magnetic EVs for image-guided therapy. She is currently a tenured CNRS researcher and works on EVs engineered with nanoparticles and drugs as drug delivery vectors for cancer therapy and regenerative medicine. She has 47 publications, 2 book chapters, 6 pending patents, > 1 000 citations and a H-factor of 19.