| Abstract | Alzheimer's Disease (AD) affects over 6.5 million Americans over the age of 65. Previous research links AD with Amyloid-Beta-40 (A) aggregation in the brain, which creates neurotoxic plaques, associated with AD. A potential mechanism in the treatment of AD is using therapeutics that will prevent the formation of these plaques, which is possible with Metal ion chelation therapy.
Metal ion chelation therapy ideally stops metal ions from aiding in the aggregation of A. However, to deliver metal chelating agents to the brain, a drug-delivery mechanism is required that will be able to deliver this potential therapeutic across the Blood-Brain Barrier. Mesoporous silica is a potential drug delivery material due to its small particle size, high loading capacity, surface tunability, and biocompatibility. Along with these characteristics, mesoporous silica can create a sustained release profile of a given therapeutic, allowing for a slow and steady release profile, reducing the risks of medication side effects.
This project seeks to establish the optimal loading capacities of a class of potential metal ion chelate therapeutic molecules known as pyclens into mesoporous silica, each with different pyridyl moieties and chemical functionalities along the rim of the molecule. Loading capacity measurements for these pyclen derivatives reveal loading percentages in the 10-25% range, varying by pyclen identity. Additionally, release studies monitored diffusion over time to find which pyclen molecule achieved "sustained" ll loaded pyclen species were able to show sustained release after 20 minutes, both in the presence and absence of copper metal ions (Cu2+). Turbidity assays with A present showed that all pyclen species decreased protein aggregation in the presence of Cu2+ metal ions, relative to non-pyclen controls, showing that all pyclen species were able to successfully prevent the aggregation of A in the presence of Cu2+ metal ions. |
