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 Young Investigator Award 2022
University of Paris-Saclay, France Title:”Characterization and evaluation of hybrid systems composed of hyaluronic acid and liposomes for the transtympanic administration of an antioxidant for cochlear implantation” Supervisors: Prof. Amélie Bochot and Prof. Florence Agnely (University of Paris-Saclay)
Abstract PhD thesis
Nowadays, patients suffering from It showed the impact of liposome surface and size deafness with residual hearing could benefit from on the microstructure of these hybrid systems and cochlear implantation. However, the insertion of this on release mechanisms. Then, NAC encapsulation device can damage cochlear structures and induce an in liposomes was optimized to avoid its oxidative stress harmful for sensory cells. To protect degradation in N,N’diacetyl-L-cystine (DiNAC) and the inner ear from this trauma, this thesis describes comply with transtympanic injection criteria. In the encapsulation of an antioxidant, N-acetyl-L- guinea pigs, the liposomal gel allowed NAC release cysteine (NAC), in a formulation adapted for in the inner ear fluids for 15 days. Nevertheless, an transtympanic injection. For this purpose, we unexpected ototoxicity was observed in both developed hybrid systems composed of liposomes implanted and non-implanted animals. DiNAC was dispersed in a hyaluronic acid network. A physico- quantified in the inner ear in higher proportion chemical study of these systems by small-angle than NAC. The production of glutathione and its neutron scattering and of liposome release by oxidized form was not stimulated. Transwell® diffusion cell was performed.
It showed the impact of liposome surface and size on the microstructure of these hybrid systems and on release mechanisms. Then, NAC encapsulation in liposomes was optimized to avoid its degradation in N,N’diacetyl-L-cystine (DiNAC) and comply with transtympanic injection criteria. In guinea pigs, the liposomal gel allowed NAC release in the inner ear fluids for 15 days. Nevertheless, an unexpected ototoxicity was observed in both implanted and non-implanted animals. DiNAC was quantified in the inner ear in higher proportion than NAC. The production of glutathione and its oxidized form was not stimulated.
APGI Young Investigator 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.