Preeclampsia (PE) is a potentially lethal orphan-drug pregnancy complication characterized by high blood pressure and endothelial damage, affecting multiple organs and with devastating consequences for mother and child. The main objective of the project is the study of the effectiveness of antioxidant therapies in a rat model that mimics characteristics of PE, and make progress towards the clinical application of new antioxidant and anti-inflammatory strategies. All aspects of efficacy and efficiency, pharmacokinetics and pharmacodynamics, biodistribution, safety and therapeutic effects will be central. Methodology: Antioxidants have limited absorption profiles, low bioavailability and low concentrations at the target site. Nanotechnology has shown us recently how antioxidant nanoparticles (NP) (especially CeO2NPs) are powerful anti-inflammatory agents that contribute to treat many inflammations related diseases. CeO2NPs displaying minimal toxicity to normal tissues while providing cellular protection from various forms of ROS and irradiation have caught considerable attention as a potential therapeutic tool in the prevention and treatment of oxidative stress-related diseases. Nanocarriers do not cross endothelial barriers, therefore allow treating the mother and not the child. Liposomes, and derivate emulsionated formulations carrying antioxidants, including CeO2NPs, or CeO2NPs alone, or CeO2NPs conjugated to the placental growth factor (PLGF), for targeting and therapy, will be prepared, and their stability and physicochemical evolution will be evaluated in different media. In addition, the penetrability, intracellular localization, toxicity and antioxidant capacity of the new formulated antioxidants will be determined in primary cells derived from human placenta, ex vivo tissue and in vivo models. A formulation will be developed for intravenous application, and finally the therapeutic action in the progression of PE in the animal model will be evaluated.
Preeclampsia
nanotecnología
antioxidantes
01/01/2021 - 31/12/2023
ELENA CARRERAS MORATONAS
FUNDACION INSTITUTO DE INVESTIGACION VALLE DE HEBRON
HOSPITAL VALLE DE HEBRON
CATALUÑA
BARCELONA
111,320 €