Extracellular vesicle production and engineering by turbulence for fistula therapy in thermoreversible hydrogels

The ERC Starting Grant project ExocyTher focuses on a cell-free therapy for digestive fistulas related to Crohn's disease. The aim is to investigate extracellular vesicles (EVs) released by stromal cells. The project proposes the concepts of (i) turbulence vesiculation for high-yield and large-scale EV production in bioreactors and (ii) thermo-controlled local EV delivery at the fistula.

  • Coordinator: Amanda Silva (Brun)

The Project

Digestive fistulas are a major health burden related to Crohn's disease or secondary to surgery, cancer therapy or trauma. Digestive fistulas are an abnormal communication between two digestive organs or a digestive organ and the skin representing challenging conditions associated with low remission rates and high refractoriness. There is an urgent need of novel therapeutic approaches for this disease. Such unmet needs in digestive fistula management motivated the investigation of cell therapy based on the local administration of stromal cells (SCs). These cells display multiple therapeutic effects and one of the main ones is to reduce the inflammation favoring the fistula healing process. Although cell therapy results are encouraging, they are not fully satisfactory in terms of percentage of patients that achieve log-term disease remission, leaving place for a second generation therapy. SCs are known to release pro-survival and anti-inflammatory signals by means of extracellular vesicles (EVs) pointing out EV role in regenerative medicine. The ExocyTher project investigates an alternative to cell therapy approach, by proposing a minimally-invasive cell-free local therapy based on the regenerative effect of EVs from SCs. Formerly regarded as a “cell dust”, EVs, specially from SCs, are now considered as regenerative agents able to play an important role in the healing process. Previous studies showed the beneficial effect of SC EVs in the therapy of heart, kidney, liver, brain and skin injuries (Figure 1). We consider that SC EVs represent an eligible alternative for fistula therapy, as they recapitulate the regenerative effect of their mother cells while mitigating risks of uncontrolled replication and differentiation while offering “off-the-shelf”, storage and shelf-life gains. Our previous results in a clinically relevant fistula disease model clearly indicated that a therapy based on SC EVs was able to promote post-surgical digestive fistula healing.

Today, the main challenges for rendering EV-based regenerative medicine clinically feasible are large-scale high-yield standardized EV production and EV optimized administration. Concerning EV manufacturing, stringent requirements must be considered such as up-scaled and high-yield production fulfilling uniformity, consistency, purity and reproducibility criteria based on standardized and reliable quality control and compliance to good manufacturing practices (GMP). The way EVs are administered also represents a main concern considering that systemic administration results in rapid EV clearance and localization in off-target organs.

The ExocyTher project has the ambition to render viable the implementation of EV-based therapy by tackling EV production and administration technical barriers.

Fig. 1: Regenerative effect of SC EVs may be expected for a multiple organs based on pre-clinical data.

ExocyTher proposes large-scale high-yield EV production based on our patented concept of turbulence-vesiculation complying with a standardized production in GMP bioreactors in line with regulatory issues. ExocyTher set-up relies on the generation of a controlled turbulent flow in which turbulence microvortices will elicit a shear stress on cells triggering EV release (Figure 2). Our approach is bio-inspired based on EV release by the turbulent flow in bloodstream. This turbulence-based strategy is (i) time-saving enabling massive EV release in some hours, (ii) integrated as it is based on tuning the own GMP bioreactor stirring system, (iii) straightforward as no further processing is required to eliminate the trigger (turbulence disappearing when stirring is turned off) and (iv) scalable based on turbulence physical laws.

Fig. 2: Bio-inspired EV production by a turbulent flow in a bioreactor containing microcarrier-anchored cells. EVs are naturally released in our bloodstream in response to shear stress in blood vessels. In the ExocyTher project, stomal cells are sheared by turbulence-generated microvortices triggering EV release in bioreactors.

ExocyTher also proposes a thermo-actuated EV delivery in the fistula tract (Figure 3) for eliciting an enhanced therapeutic effect in situ. ExocyTher strategy is expected to avoid systemic administration clearance and overcome difficulties related to local delivery, such as fistula secretions (washing-out the therapeutic agent) and fistula tract inaccessibility (sometimes irregular large defects of several centimeters). ExocyTher relies on dual biomaterial/EV component for fistula therapy. The thermoresponsive hydrogel biomaterial component is expected to cope with fistula local delivery difficulties promoting an occlusive effect, retaining EVs in the fistula tract and preventing EV wash-out by fistula secretions, while enabling the filling of the entire fistula tract despite its size and irregular morphology. Biomaterial choice was based on material physical and therapeutic properties and considered a clinical translation perspective. Building on strong preliminary results, we intend to investigate the combination of turbulence EVs with a poloxamer 407 hydrogel. ExocyTher proposes the off-label use of this hydrogel, which was a vessel occlusive medical device authorized in Europe, as an innovative fistula occlusive EV vehicle. This mechanical occlusive effect has an interest by itself in the therapy of digestive fistulas. Healing process is favored by decreasing the flow of secretions from the digestive system to the skin. Therefore, ExocyTher relies on a potential synergic effect of SC EVs and the thermoresponsive gel association.

ExocyTher fully considers key regulatory and manufacturing issues in the project choices to set the basis for implementing the first future clinical trial on SC EVs in a biomaterial for the therapy of digestive fistulas. Noteworthy, ExocyTher approaches may be extended to a multitude of EV parent cell types, or therapy indication. Therefore, the advances to be achieved in this project may also be relevant for unmet needs related to other diseases. We hope that the ExocyTher project may contribute in the future to democratize EVs as biotherapies for the management of digestive fistulas and other diseases with high morbidity or mortality. In a long-term perspective, by facilitating patient access to last generation therapies, ExocyTher technologies may improve the quality of life of refractory patients, tackling medical and societal challenges.

Fig. 3: Digestive fistula thererapy by extracellular vesicles into a thermo-responsive gel delivered locally at the digestive fistula.

The coordinator


Amanda K. A. Silva (Brun) obtained a Pharmacy degree in 2005, a PhD on Pharmaceutical Technology in 2008 and a second PhD in Cellular and Molecular Biology in 2010. In 2013, Amanda obtained a tenured CNRS researcher position. She works on extracellular vesicles and stimulus-responsive nanomaterials for regenerative medicine and antitumor therapy. Amanda has authored 55 papers and 8 patents.

Amanda K. A. Silva (Brun)


2007-2010 PhD on Cellular and Molecular Biology - Université d’Evry /Généthon - Partnership with Faculté de Pharmacie, Université Paris 5, France (awarded with highest honours);
Supervisors: Otto Wilhelm Merten and Daniel Scherman;
Topic: Thermoresponsive hydrogels for actuated cell attachment and detachment;
2006-2008 PhD on Pharmaceutical Technology - Health Sciences - Universidade Federal do Rio Grande do Norte, Department of Biosciences, Natal, Brazil;
Supervisors: Artur da Silva Carriço, Socrates Tabosa do Egito;
Topic: Gastro-resistant polymer-coated magnetic systems for oral route administration;
2005-2006 MSc on Pharmaceutical Technology - Universidade Federal do Rio Grande do Norte, Department of Biosciences, Natal, Brazil;
Supervisors: Artur da Silva Carriço, Socrates Tabosa do Egito;
Topic: Design and characterization of micro-clusters of superparamagnetic nanoparticles;
2001-2005 Pharmacy degree - Universidade Federal do Rio Grande do Norte, Department of Pharmacy, Natal, Brazil;
2013-current Invited lecturer - Nanoscale approaches for regenerative medicine / evaluation of MSc student projects: 15 h/year, Biomedical Engineering Master's Degree Program, Université Paris Descartes and Paris Institute of Technology (ParisTech), Paris, France;
2011-current Invited lecturer - Magnetic nanoparticles for MRI for MSc students: 3 h/year, Master 1, UE 23 (Health track), Faculté de Medicine, Université Paris 7, Paris, France;
2009-2010 Volunteer monitor - Pharmaceutical Technology for undergraduate students: 50 h/year, Faculté de Pharmacie, Université Paris 5, Paris, France;
2007-2009 Tutor – English for undergraduate students: 80 h/year, Université d’Evry, Evry, France;
2005-2006 Lecture trainee - Pharmaceutical Technology for undergraduate students: 100 h/year, Universidade Federal do Rio Grande do Norte, Department of Pharmacy, Natal, Brazil;
2013 Post-doctoral fellow - Laboratoire Hémostase, Bio-ingénierie et Pathologies Cardiovasculaires, INSERM U698, Université Paris 7, Université Paris 13;
Topic: Nanobiosystems for therapy of cardiovascular pathologies (D. Letourneur’s team);
2010 – 2012 Post-doctoral fellow - Laboratoire "Matière et Systèmes Complexes", Physics Department, Université Paris 7, CNRS, Paris, France;
Topic: Extracellular vesicles for theranosis (C. Wilhelm and F. Gazeau’s team);
2020 Co-coordinator of the organising committee - EV thematic school, La Grande Motte, France
2019 Member of the organising committee - Annual Meeting of the French Society for Nanomedicine (SFNano); 400 attendees; Dijon, France;
2018 Coordinator - French-Brazilian Workshop on Nanomedicine; 30 attendees, Paris
2017 Member of the local organising committee - 1st Annual Meeting of the French Society of Extracellular Vesicles (FSEV); 200 attendees; France;
2017 Vice-coordinator of the French-Brazilian Workshop on Nanomedicine; 50 attendees, France;
2016 Coordinator of the local organising committee - 3rd Annual Meeting of the French Society for Nanomedicine (SFNano); 230 attendees; Paris, France;
2016 Member of the organising committee - the Biannual MSC lab Scientific Meeting; 80 attendees, Saint-Valery-sur-Somme, France;
2015 Coordinator - the French-Brazilian Workshop on Nanomedicine; 20 attendees, Natal, Brazil;
2012 Member of the local organising committee of the "Journées du Groupe Thématique de Recherche sur les Vecteurs – GTRV", 130 attendees; France;
Current Editorial board member of Pharmaceutical Nanotechnology; Journal of Nanotechnology in Diagnosis and Treatment and International Journal of Molecular Sciences;
Invited guest editor of Advanced Drug Delivery Reviews (IF 13.3);
Evaluator, Cancéropôle Nord-Ouest, France; Agence nationale de la recherché, ANR, France; Dutch Technology Foundation funding agency, The Netherlands; Service de Santé des Armées, France;
Reviewer for the Journal of controlled Release, Theranostics, Journal of Visualized Experiments, Colloids and Surfaces B: Biointerfaces, Cytotechnology, Journal of Drug Delivery Science and Technology, Scientific Reports, Carbon, ACS Nano, etc;
2013-current Elected board member of French Society for Nanomedicine (SFNano) (youngest board member)
2015-2018 Research and Teaching Excellence Award (4-year duration), CNRS
2020-current Co-founder of Evora Biosciences – Scientific advisor
2019-current Co-founder of EverZom – Scientific advisor


  • 1. Exosomes: A Novel Therapeutic Paradigm for Treatment of Depression. Bhatt S, Kanoujia J, Dhar AK, Arumugam S, Silva AKA, Mishra N, Current Drug Targets, 2020, accepted
  • 2. 3D Magnetic Alignment of Cardiac Cells in Hydrogels. Richard S†, Silva AKA†, Mary G, Ragot H, Perez JE, Ménager C, Gazeau F, Boucenna I, Agbulut O, Wilhelm C, ACS Applied Bio Materials, 2020, accepted († Equal contribution).
  • 3. Enhancing digestive fistula healing by the off-label use of a thermoresponsive vessel occluder polymer associated with esophageal stent placement: a case report. Berger A, Chaudron E; Boucenna, I, Gazeau F, Wilhelm C, Cellier C, Clément O, Silva AKA†; Rahmi G†. Clinics and Research in Hepatology and Gastroenterology. 2020, in press. https://doi.org/10.1016/j.clinre.2020.06.001. († Equal contribution)
  • 4. Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis. Neveu G, Richard C, Dupuy F, Behera PK, Volpe F, Subramani PA, Marcel-Zerrougui B, Vallin P, Andrieu M, Minz AM, Azar N, Martins RM, Lorthiois A, Gazeau F, Lopez-Rubio JJ, Mazier D, Silva AKA, Satpathi S, Wassmer S, Verdier F, Lavazec C. Blood. 2020 136 (12): 1381 (Impact factor: 17.5).
  • 5. mTHPC-loaded Extracellular Vesicles significantly improve mTHPC diffusion and photodynamic activity in preclinical models. Millard M, Posty S, Piffoux M, Jasniewski J, Lassalle H-P, Yakavets I, Gazeau F, Wilhelm C, Silva AKA, Bezdetnaya L. Pharmaceutics 2020, 12(7), 676.
  • 6. High yield and scalable EV production from suspension cells triggered by turbulence in a bioreactor. Grangier A, Wilhelm C, Gazeau F, Silva AKA. Cytotherapy. 2020, 22(5), 50.
  • 7. Physically-triggered nanosystems for therapy and diagnosis. Wilhelm C, Gazeau F, SILVA AKA. Adv Drug Deliv Rev 2019, 138, 1-2 (Impact factor 13.3).
  • 8. Iron Oxide Nanoflowers @ CuS Hybrids for Cancer Tri-Therapy: Interplay of Photothermal Therapy, Magnetic Hyperthermia and Photodynamic Therapy. Curcio A, Silva AKA, Cabana S, Espinosa A, Baptiste B, Menguy N, Wilhelm C, Abou-Hassan A. Theranostics 2019; 9(5):1288.
  • 9. Extracellular vesicles for personalized medicine: The input of physically triggered production, loading and theranostic properties. Piffoux M, Nicolás-Boluda A, Mulens-Arias V, Richard S, Rahmi G, Gazeau F, Wilhelm C, Silva AKA. Adv Drug Deliv Rev 2019, 138, 247 (Impact factor 13.3).
  • 10. mTHPC-loaded extracellular vesicles outperform liposomal and free mTHPC formulations by an increased stability, drug delivery efficiency and cytotoxic effect in tridimensional model of tumors. Millard M, Yakavets I, Piffoux M, Silva AKA, Gazeau F, Guigner J-M, Jasniewski J, Lassalle H-P, Wilhelm C, Bezdetnaya L. Drug Delivery. 2018, 25, 1790.
  • 11. Direct imaging of capillaries reveals the mechanism of arteriovenous interlacing in the chick chorioallantoic membrane. Richard S, Silva AKA, Tedesco A, Gallois B, Taghi N, Dantan P, Seguin J, Fleury V. Communications Biology. 2018, 235.
  • 12. Thermoresponsive Gel Embedding Adipose Stem Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy. Silva AKA, Perretta S, Perrod G, Pidial L, Lindner V, Carn F, Lemieux S, Alloyeau D, Boucenna I, Menasché P, Dallemagne B, Gazeau F, Wilhelm C, Cellier C, Clément O, Rahmi, G. ACS Nano. 2018, 12(10):9800-9814 (Impact factor 14.5).
  • 13. Theranostic Iron Oxide Nanoparticle Cargo Defines Extracellular Vesicle‐Dependent Modulation of Macrophage Activation and Migratory Behavior. Mulens‐Arias V, Nicolás‐Boluda A, Silva AKA, Gazeau F. Advanced BioSystem 2018, 2, (9) 1800079.
  • 14. Intracellular Biodegradation of Ag Nanoparticles, Storage in Ferritin, and Protection by Au Shell for Enhanced Photothermal Therapy. Espinosa A, Curcio A, Cabana S, Radtke G, Bugnet M, Kolosnjaj-Tabi J, Péchoux C, Alvarez-Lorenzo C, Botton GA, Silva AKA, Abou-Hassan A, Wilhelm C. ACS nano 2018, 12, 6523 (Impact factor 14.5).
  • 15. Physical oncology: New targets for nanomedicine. Nicolas-Boluda A, Silva AKA, Fournel S, Gazeau F. Biomaterials. 2018, 150, 87 (Impact factor 10.3).
  • 16. Magnetic (hyper)thermia or photothermia? Progressive comparison of iron oxide and gold nanoparticles heating in water, in cells, and in vivo. Espinosa A, Kolosnjaj-Tabi J, Abou-Hassan A, Plan Sangnier A, Curcio A, Silva AKA, Di Corato R, Neveu S, Pellegrino T, Liz-Marzán LM, Wilhelm C. Advanced Functional Materials. 2018, 1803660 (Impact factor of 16.8).
  • 17. Targeted thermal therapy with genetically engineered magnetite magnetosomes@RGD: Photothermia is far more efficient than magnetic hyperthermia. Plan A, Preveral S, Curcio A, Silva AKA, Lefèvre CT, Pignol D, Lalatonne Y, Wilhelm C. Journal of Controlled Release 2018, 279, 271.
  • 18. Modification of Extracellular Vesicles by Fusion with Liposomes for the Design of Personalized Biogenic Drug Delivery Systems. Piffoux M, Silva AKA, Wilhelm C, Gazeau F, Tareste D. ACS Nano. 2018, 12, 6830 (Impact factor 14.5).
  • 19. Monitoring the dynamics of cell-derived extracellular vesicles at the nanoscale by liquid-cell transmission electron microscopy. Piffoux, M, Ahmad, N, Nelayah, J, Wilhelm, C, Silva AKA, Gazeau, F, Alloyeau, D. Nanoscale 2018, 10, 1234.
  • 20. Nanoparticle-based hyperthermia, a local treatment modulating the tumor extracellular matrix. Kolosnjaj-Tabi J, Marangon, I, Nicolas-Boluda, A, Silva AKA, Gazeau F. Pharmacological Research 2017, 126, 123.
  • 21. Extracellular Vesicle Production Loaded with Nanoparticles and Drugs in a Trade‐off between Loading, Yield and Purity: Towards a Personalized Drug Delivery System. Piffoux M, Silva AKA, Lugagne JB, Hersen P, Wilhelm C, Gazeau F. Drug Delivery: Extracellular Vesicle Advanced Biosystems. 2017, DOI: 10.1002/adbi.201700044
  • 22. Overcoming the tumor microenvironment: The role of nanohyperthermia. Silva AKA, Nicolas-Boluda A, Fouassier L, Gazeau F. Nanomedicine 2017, 12 (11) :1213.
  • 23. Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy. Marangon I, Silva AKA, Guilbert T, Kolosnjaj-Tabi J, Marchiol C, Natkhunarajah S. Theranostics. 2017, 7(2)329.
  • 24. Design of Magnetic Polymeric Particles as a Stimulus-Responsive System for Gastric Antimicrobial Therapy. Silva-Freitas EL, Pontes TRF, Araújo-Neto RP, Damasceno ÍHM, Silva KL, Carvalho JF, Medeiros AC, Silva RB, Silva AKA, Morales MA, Egito EST, Dantas AL, Carriço AS. AAPS PharmSciTech. 2017, 18(6), 2026.
  • 25. Designing 3D mesenchymal stem cell sheets merging magnetic and fluorescent features: When cell sheet technology meets image-guided cell therapy. Rahmi G, Pidial L, Silva AKA, Blondiaux E, Meresse B, Gazeau F, Autret G, Balvay D, Cuenod CA, Perretta S, Tavitian B, Wilhelm C, Cellier C, Clément O. Theranostics. 2016, 6(5), 739.
  • 26. Synergic mechanisms of photothermal and photodynamic therapies mediated by photosensitizer/carbon nanotube complexes. Marangon I, Ménard-Moyon C, Silva AKA, Bianco A, Luciani N, Gazeau F. Carbon. 2016, 97, 110.
  • 27. Cancer Cell Internalization of Gold Nanostars Impacts Their Photothermal Efficiency In Vitro and In Vivo: Toward a Plasmonic Thermal Fingerprint in Tumoral Environment. Espinosa A, Silva AKA, Sánchez-Iglesias A, Grzelczak M, Péchoux C, Desboeufs K, Liz-Marzán LM, Wilhelm C.. Advanced Healthcare Materials. 2016, 5(9), 1040.
  • 28. Massive release of extracellular vesicles from cancer cells after photodynamic treatment or chemotherapy. Aubertin K, Silva AKA, Luciani N, Espinosa A, Djemat A, Charue D, Gallet F, Blanc-Brude O, Wilhelm C. Scientific Reports. 2016, 6:35376.
  • 29. Magnetic drug carriers: Bright insights from light-responsive magnetic liposomes. Silva AKA, Ménager C, Wilhelm C. Nanomedicine. 2015, 10(18), 2797.
  • 30. Combining magnetic nanoparticles with cell derived microvesicles for drug loading and targeting. Silva AKA, Luciani N, Gazeau F, Aubertin K, Bonneau S, Chauvierre C, Letourneur D, Wilhelm C. Nanomedicine: Nanotechnology, Biology, and Medicine. 2015, 11(3):645.
  • 31. Polysaccharide-based strategies for heart tissue engineering. Silva AKA, Juenet M, Meddahi-Pellé A, Letourneur D. Carbohydrate Polymers. 2015, 116, 267.
  • 32. Combining magnetic hyperthermia and photodynamic therapy for tumor ablation with photoresponsive magnetic liposomes. Di Corato R, Béalle G, Kolosnjaj-Tabi J, Espinosa A, Clément O, Silva AKA, Ménager C, Wilhelm C. ACS Nano. 2015, 9(3):2904-16 (Impact factor 14.5).
  • 33. Polysaccharide nanosystems for future progress in cardiovascular pathologies. Silva AKA, Letourneur D, Chauvierre C. Theranostics. 2014, 4(6), 579.
  • 34. Heat-generating iron oxide nanocubes: Subtle "destructurators" of the tumoral microenvironment. Kolosnjaj-Tabi J, Di Corato R, Lartigue L, Marangon I, Guardia P, Silva AKA, Luciani N, Clément O, Flaud P, Singh JV, Decuzzi P, Pellegrino T, Wilhelm C, Gazeau F. ACS Nano. 2014, 8(5), 4268 (Impact factor 14.5).
  • 35. Strong and specific interaction of ultra-small superparamagnetic iron oxide nanoparticles and human activated platelets mediated by fucoidan coating. Bachelet-Violette L, Silva AKA, Maire M, Michel A, Brinza O, Ou P, Véronique Ollivier, Nicoletti A, Wilhelm C, Letourneur D, Ménager C, Chaubet F. RSC Advances. 2014, 4(10), 4864.
  • 36. Xyloglucan-derivatized films for the culture of adherent cells and their thermocontrolled detachment: A promising alternative to cells sensitive to protease treatment. Silva AKA, Richard C, Ducouret G, Bessodes M, Scherman D, Merten OW. Biomacromolecules. 2013, 14(2):512.
  • 37. Magnetic and photoresponsive theranosomes: Translating cell-released vesicles into smart nanovectors for cancer therapy. Silva AKA, Kolosnjaj-Tabi J, Bonneau S, Marangon I, Boggetto N, Aubertin K, Clément O, Bureau MF, Luciani N, Gazeau F, Wilhelm C. ACS Nano. 2013, 7(6):4954 (Impact factor 14.5).
  • 38. Impact of photosensitizers activation on intracellular trafficking and viscosity. Aubertin K, Bonneau S, Silva AKA, Bacri JC, Gallet F, Wilhelm C. PLoS ONE. 2013, 8(12).
  • 39. Cell-derived vesicles as a bioplatform for the encapsulation of theranostic nanomaterials. Silva AKA, Di Corato R, Pellegrino T, Chat S, Pugliese G, Luciani N, Gazeau F, Wilhelm C. Nanoscale. 2013, 5(23):11374.
  • 40. Cellular transfer of magnetic nanoparticles via cell microvesicles: Impact on cell tracking by magnetic resonance imaging. Silva AKA, Wilhelm C, Kolosnjaj-Tabi J, Luciani N, Gazeau F. Pharmaceutical Research. 2012, 29(5):1392.
  • 41. Magnetophoresis at the nanoscale: Tracking the magnetic targeting efficiency of nanovectors. Silva AKA, Di Corato R, Gazeau F, Pellegrino T, Wilhelm C. Nanomedicine. 2012, 7(11):1713.
  • 42. Amphotericin B microemulsion reduces toxicity and maintains the efficacy as an antifungal product. Damasceno BPGL, Dominici VA, Urbano IA, Silva JA, Araújo IB, Santos-Magalhães NS, Silva AKA Medeiros AC, Oliveira GA, Egito EST. Journal of Biomedical Nanotechnology. 2012, 8(2):290.
  • 43. Cell microcarriers and microcapsules of stimuli-responsive polymers. Silva AKA, Richard C, Bessodes M, Scherman D, Merten OW. Journal of Controlled Release. 2011, 149(3):209.
  • 44. Drug targeting and other recent applications of magnetic carriers in therapeutics. Silva AKA, Silva EL, Carvalho JF, Pontes TRF, Neto RPDA, Carriço ADS, Egito EST. Key Engineering Materials 2010. 357.
  • 45. Study on the sol-gel transition of xyloglucan hydrogels. Silva AKA, Richard C, Bessodes M, Scherman D, Narita T, Ducouret G, Merten OW. Carbohydrate Polymers. 2010, 80(2):556.
  • 46. Thermoresponsive surfaces for cell culture and enzyme-free cell detachment. Silva AKA, Richard C, Bessodes M, Scherman D, Merten OW. Progress in Polymer Science. 2010, 35(11):1311 (Impact factor: 22.6).
  • 47. The effect of sterilization methods on the thermo-gelation properties of xyloglucan hydrogels. Silva AKA, Richard C, Bessodes M, Scherman D, Narita T, Ducouret G, Merten OW. Polymer Degradation and Stability. 2010, 95(2):254.
  • 48. Stationary cuvette: A new approach to obtaining analytical curves by UV-VIS spectrophotometry. Silva KGH, Xavier Jr FH, Farias IEG, Silva AKA, Caldas Neto JA, Souza LCA, Santiago RR, Junior A, Soares LAL, Santos-Magalhaes N, Egito EST. Phytochemical Analysis. 2009, 20(4):265.
  • 49. Growth factor delivery approaches in hydrogels. Silva AKA, Richard C, Bessodes M, Scherman D, Merten OW. Biomacromolecules. 2009, 10(1):9.
  • 50. Development of superparamagnetic microparticles for biotechnological purposes. Silva AKA, Egito EST, Nagashima Jr T, Araújo IB, Silva ÉL, Soares LAL, Carriço A. Drug Development and Industrial Pharmacy. 2008, 34(10):1111.
  • 51. Magnetic carriers: A promising device for targeting drugs into the human body. Silva AKA, Silva ÉL, Carriço AS, Egito EST. Current Pharmaceutical Design. 2007, 13(11):1179.
  • 52. Synthesis and characterization of xylan-coated magnetite microparticles. Silva AKA, da Silva EL, Oliveira EE, Nagashima Jr T, Soares LAL, Medeiros AC, Araújo JH, Araújo IB, Carriço AS, Egito EST. International Journal of Pharmaceutics. 2007, 334(1-2):42.
  • 53. SolEmuls® technology: A way to overcome the drawback of parenteral administration of insoluble drugs. Junghanns JU, Buttle I, Müller RH, Araújo IB, Silva AKA, Egito EST, Damasceno BPGL. Pharmaceutical Development and Technology. 2007, 12(5):437.
  • 54. Influence of a lipophilic drug on the stability of emulsions: An important approach on the development of lipidic carriers. Formiga FR, Fonseca IAA, Souza KB, Silva AKA, Macedo JPF, Araújo IB, Soares LAL, Egito EST. International Journal of Pharmaceutics. 2007, 344(1-2):158.
  • 55. A new insight about pharmaceutical dosage forms for benzathine penicillin. Silva KGHE, Xavier-Júnior FH, Farias IG, Neto J, Silva AKA, Nakashima-Júnior T, Araújo, IB, Oliveira A, Medeiros AC, Egito, EST. Journal of Basic and Applied Pharmaceutical Sciences. 2006, 27, 21.
  • 56. Safety concerns related to magnetic field exposure. Silva AKA, Silva ÉL, Egito EST, Carriço AS. Radiation and Environmental Biophysics. 2006, 45(4):245.

Key collaborators

ExocyTher project is based at the laboratory Matière et Systèmes Complexes (Université de Paris, CNRS) in close collaboration with Drs. Florence Gazeau, Dr. Nathalie Luciani and Claire Wilhelm. The main partner is Prof. Dr. Gabriel Rahmi, gastro-enterologist (Hôpital Européen Georges Pompidou, PARCC, INSERM U970, Université de Paris). Dr. Sebastien Banzet, Dr. Christophe Martinaud (CTSA) and Dr. Noëlle Mathieu (IRSN) are also important partners.

Prof. Gabriel Rahmi

Dr. Claire Wilhelm

Dr. Florence Gazeau

Dr. Noëlle Mathieu