Background
Alzheimer's disease (AD) is an irreversible, progressive neurological brain disorder that slowly destroys the memory and thinking skills in people, and, eventually, their ability to carry out the simplest tasks. Estimates vary, but experts suggest that more than 5.5 million Americans, most of them age 65 or older, may have dementia caused by Alzheimer's. Currently there is no known cure or preventative measure for this disease. One of the main features associated with AD is the abnormal buildup of clumps within the brain called amyloid plaques derived from the aggregation of amyloid beta (Aβ) proteins. Aβ is a small piece of a larger protein called "amyloid precursor protein" (APP). When APP is "activated" to do its normal job, it is cut by other proteins into separate, smaller sections where portions stay inside and outside cells. In short, there are two major pathways in which this chain cleavage can occur, one that leads to a non-amyloidogenic pathway and one that leads to the amyloidogenic Aβ protein. By enhancing the activity of a disintegrin metalloproteinase 10 (ADAM10), the former pathway is enhanced and the Aβ protein generation is mitigated. Gallic acid is known ADAM10 activator.
Approach
The approach for this project is to formulate drug loaded, stable, blood-brain barrier (BBB) targeting liposome formulations and to develop an experimental model that can precisely evaluate the delivery of those liposome-nanoparticles based on the interaction of the BBB and liposome-nanoparticles. The novelty associated with this work includes: the unique combination of delivery vehicle and active pharmaceutical ingredient (gallic acid) and the type of computational modelling employed. The numerical simulation described here will model the details of the geometry of the liposomes, based on characterization of the formulations prepared, and BBB, based on literature provided information, with a great deal of accuracy using CFD commercial software COMSOL Multiphysics.
Accomplishments
- Prepared nano-sized (<200 nm) liposomes from biocompatible materials.
- Prepared liposomes with ADAM-10 activator gallic acid.
- Performed initial stability studies.
- Completed the initial computational model development for liposome transport across the BBB using simplified geometry which will be extended to complex geometries.