Exploring the efficacy of nanoparticles for Alzheimer's disease treatment

Abstract

Alzheimer’s disease (AD) is a proteinopathy characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles composed of Amyloid beta (Aβ) peptides and hyperphosphorylated Tau protein. AD affects 50 million people worldwide with an annual cost of US$ 1 trillion, AD remains a significant challenge due to the ineffectiveness of current therapeutic strategies. The main obstacle for developing effective therapies for AD is the presence of a tight and selectively permeable blood-brain barrier (BBB) that prevents most molecules, including antibodies, from entering the brain. Drawing from our prior work, we've established the ability of our single-domain antibodies PrioV3 to traverse the blood-brain barrier (BBB) by exploiting clathrin-mediated transcytosis in vivo. Nevertheless, following intraperitoneal administration, significant quantities of these antibodies were identified in peripheral organs, including the liver and kidneys. As a biopolymer, Chitosan possesses unique properties such as ultra-low toxicity and capability of surface modification for encapsulation of molecules and surface coating. In order to enhance BBB transport of larger quantities of single domain antibodies and other molecules, we developed and characterised a robust and highly reproducible chitosan based nano carrier system. The results of this thesis are discussed in chapter 3,4 and 5 respectively.

Date of Award	2024
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Mourad Tayebi (Supervisor) & Feng Li (Supervisor)