Nanoparticles as a vehicle for a novel neuroprotective drug to fight Alzheimer's disease

Alzheimer’s disease (AD) is a neurodegenerative disease and the leading cause of dementia worldwide. To date, the therapies on the market for this disease are limited. This is due to, among many reasons, the difficulties in understanding completely the causes of the disease and the presence of the blood-brain barrier, a semipermeable border that prevents the entrance of solutes into the central nervous system. Therefore, the need to study new approaches for the targeted delivery of therapeutics to the brain. In recent years, nanoparticles able to transport molecules across the blood-brain barrier have gained attention and are a promising approach for the targeted delivery of therapeutics to the brain. This project intended to develop nanoparticles to encapsulate compounds for AD therapy. The nanoparticles were characterized through their size, polydispersity index, zeta potential and encapsulation efficiency. Different types of nanoparticles produced by different methods were studied: poly(lactic-co-glycolic acid) (PLGA) nanoparticles - with a focus on both oral and nose-to-brain delivery – and solid lipid nanoparticles. PLGA nanoparticles produced by the double emulsion method showed to have good and stable size and zeta potential over the time of the study; however, the encapsulation efficacy of a hydrophilic compound in these particles was low. With the protocol to produce PLGA nanoparticles through a single emulsion, it was possible to obtain nanoparticles with a mean diameter of 239.4 nm, a polydispersity index of 0.108 and a zeta-potential of -19.3 mV. A mean diameter close to 200 nm increases the chance for the particles to cross the blood-brain barrier, so even if the size is close to the goal, further optimization will be required. Other PLGA nanoparticles surface-modified with chitosan intended for nose-to-brain delivery were produced, having a mean diameter of 199.1 nm, a polydispersity index of 0.1075 and a zeta-potential of 6.3 mV, being suitable for the application. Lastly, the protocol to produce solid lipid nanoparticles was optimized, and it was possible to achieve particles with an average size of 236.6 nm, a polydispersity index of 0.277 and a zeta potential of -21.1 mV.