Every year, the “APGI Young Investigator Award” recognizes the most outstanding doctoral thesis in the field of Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology. It is kindly sponsored by Sanofi.
APGI Thesis Award 2021
Raoul Diaz Salmeron
University of Paris-Saclay, France
Title:”Directed-mobility and enhanced-adhesion nano-platelets for local drug delivery: towards a new treatment of bladder diseases.”
Supervisors: Prof. Gilles Ponchel and Prof. Kawthar Bouchemal (University of Paris-Saclay)
Abstract PhD thesis
Local drug delivery allows to bring large amounts of drugs with reduced side effects, in comparison with systemic administration. Despite the advantages provided by the local drug delivery, intravesical drug delivery is still challenging because it exhibited several issues which are decreasing the therapeutic efficacy and the patient compliance to the treatment. Most therapies for the treatment of bladder diseases are simple drug solutions or suspensions administered intravesically by using a catheter through the urethra in order to easily reach the bladder and, consequently, the urothelium. Since the drug is administered into the bladder, drug dilution is occurring because of the continuous production of urine. Furthermore, active substances are being eliminated during washout when bladder urine voiding is happening. These two processes lead to the decrease of local drug concentration close to the urothelium. Patients need repeated catheterization, performed by health care practitioners, to reach the therapeutic dose of the drug.
The main goal of this PhD thesis was to create and design a new nanoparticulate system with non-spherical shape susceptible to move in a different manner compared to spherical nanoparticles. These systems may exhibit an amplified mucoadhesion allowing to bring more important amounts of drug than classical and nanoparticle administration. These nanoparticles, called now nano-platelets have shown different movement behavior than the spherical ones. Indeed, they diffuse more rapidly in a straight-line way. Thanks to their oriented and directed motion and to their intrinsic properties, due to the shape, these systems have shown a better mucoadhesion on the bladder tissue, a better uptake in different cell lines and they were far less rapidly eliminated from the urothelium mucosa.
An in vivo model of Bladder Painful Syndrome / Interstitial Cystitis in rats demonstrated the therapeutic efficacy of nano-platelets, especially for hyaluronic acid nanoparticles. Indeed, they demonstrated a better bioaccumulation into the bladder and a better therapeutic efficacy as anti-inflammatory and urothelium regenerating agents.
These nanoparticulate systems represent a new innovative, rational and effective approach allowing to open new research pathways for the treatment of bladder diseases.
APGI thesis award 2020
University of Ghent, Belgium
“Laser-induced vapor nanobubbles: the golden ticket to the biofilm center”
Supervisor: Prof. Dr. Kevin Braeckmans and Prof. Dr. Tom Coenye
Abstract PhD thesis
Being listed as one of the top priorities of the World Health Organization for 2019, antimicrobial resistance has become beyond any doubt an important threat to healthcare. An important reason for the decreased sensitivity of bacteria towards antibiotics is their capability to form so-called biofilms. The increased tolerance of biofilms is multifactorial and includes the reduced penetration rate of antibiotics through dense biofilms.
In this thesis, we explored the potential of laser-induced vapour nanobubbles (VNB) formed around plasmonic nanoparticles to locally disturb biofilm integrity and improve antibiotics’ diffusion and efficiency. First, we systematically investigated the potential of VNB as an anti-biofilm approach on both Gram-negative as Gram-positive biofilms. Spurred by the promising results of this proof-of-concept study, we aimed to take the first steps towards an actual application, more specifically for the treatment of biofilm related wound infections. In the last part of this thesis, antibiotics were encapsulated inside nanocarriers that were able to generate VNB in order to achieve light-triggered release of antibiotics, thereby providing a complete solution to the biofilm diffusion barrier.