Needle-free transdermal delivery
There are various alternative routes (electrical, mechanical, thermal) for transdermal delivery to avoid the use of the injection syringe, which could improve the quality of life of patients with diseases such as diabetes. These methods include, for example, micro-needles, electro-permeabilization, and iontophoresis. Electropermeabilization allows, via the application of an electric field, to temporarily increase the permeability of the skin and consequently to allow the transdermal passage of molecules of high molecular weight.
The goal of this project is to design and realize a nanocomposite patch based on carbon nanotubes (CNT) to store, but also releasing a drug when it is subjected to electrostimulation. To do this, different polymers and different shaping techniques have been explored and developed to demonstrate the feasibility of our approach.
Transdermal delivery of fluorescent dextran by CNT nanocomposites after electrostimulation. Guillet et al, 2017. -->
Investigators: PhD student : Juliette SIMON/ Engineer: E. Bellard / Project leader : M. Golzio
Collaborations: E Flahaut (CIRIMAT, Toulouse)
Improve optical imaging: multispectral, far-red fluorescent dyes, bioluminescence and intravital imaging
Optical imaging of small animals allows observation of kinetic fluorescent events in time and space on the scale of a whole body, an organ or a cell. It enables detection and quantification of the in vivo expression of GFP (or red-shifted fluorescent protein) used to monitor gene expression, gene regulation, tumor growth and metastasis on a scale of days or weeks. Autofluorescence considerably limits sensitivity in vivo and the most efficient spectral range for fluorescence detection is between 600 and 900 nm. Therefore it is important to use fluorescent dye emitting in the far red such as Cy5, Cy5.5. As far as visible emitting fluorescent dye are used (reporter proteins), multispectral imaging and image processing will be employed in order to reduce artifacts and background signal due to tissue autofluorescence. Another technic we use to increase sensitivity and image deeper in vivo is bioluminescence. It also enables detection and quantification on several weeks of luciferase expression used, most of time, to monitor tumor growth and metastasis. Despite a lower spatial resolution it offers a very sensitive detection at the level of few cells. As fluorescence, this imaging technology is not invasive, the comfort of animals is preserved. To overcome limitations induced by the skin, we also adopted the use of intravital microscopy with the implantation of a window chamber or dorsal skinfold chamber on the back of the mice. It allows the monitoring of fluorescent cell events in the skin or a cutaneous implanted tumor on several days in the same animal. Other window models exist that enable cells monitoring in deeper orthotopic tumors like abdominal window that we want to implement for in vivo electropermeabilisation applications.
Investigators: Engineer: E. Bellard / Project leader : M. Golzio
Eradication of Sarcoids in Horses
Over the last decade, electropermeabilization has given rise to a cancer treatment modality, electrochemotherapy that combines conventional chemotherapeutic agents with electric fields . Electrochemotherapy is highly effective and is now accepted in a number of countries as a palliative treatment in Humans. In addition, electrotransfer can also be used to deliver a wide range of potentially therapeutic agents including proteins, RNA and DNA. Clinical trials of gene transfer by electric fields are still under development .
Sarcoids represent one of the main skin cancer in horses. Relapses are often present. New treatments are necessary to eradicate them. Our team has been collaborating for more than 9 years with the veterinary school in Toulouse to treat sarcoids by electrochemotherapy. The results we obtained are encouraging as more than 95% of the treated tumors are in complete regression. However, electrochemotherapy has no effect on untreated tumors. In order to eradicate all the tumors, we are now developing a new approach based on the combination of electrochemotherapy and electrogenetherapy by expressing plasmid coding IL-12 to stimulate the immune system response. This project received a prize from the Région Midi-Pyrénées Laboratory Research category in 2005.
Investigators: Researcher: M. Golzio/ Project leaders : J. Teissie and M.P. Rols
Collaborations: B. Couderc (ICR, Toulouse), Y Tamzali (ENVT, Toulouse), JB Leroy (LeroyBiotech, Saint Orens de Gameville)
Combination of ECT and EGT for sarcoid treatment. Stimulation of the immune system