11/23/2021
By Kwok Fan Chow

The Kennedy College of Science, Department of Chemistry, invites you to attend a master’s thesis defense by Coral Moretti entitled “Chemical Conjugation of Donepezil into a Glucose Carrier and Physical Complexation of Donepezil into a Small Peptide Carrier: Strategies to Enhance Bioavailability of Alzheimer’s Disease Drugs.” 

The defense will be held on Monday, Dec. 6 at noon in Olney 518, North Campus.

Committee Members:

  • Manos Gkikas (chair), Department of Chemistry, University of Massachusetts Lowell
  • Matthew Gage, Department of Chemistry, University of Massachusetts Lowell
  • Kwok-Fan Chow, Department of Chemistry, University of Massachusetts Lowell

Abstract:
Two drug delivery platforms were designed and synthesized to increase the bioavailability and effectivity of donepezil, the most used Alzheimer’s disease drug, by protecting the drug from unwanted reactions (e.g., immune system response to foreign materials) and increasing its delivery to Acetylcholinesterase, found in red blood cell and the brain. Since current donepezil delivery to the brain has been estimated to be ~5% or less, these strategies could potentially make the drug more effective and reduce unwanted side effects. Donepezil was conjugated chemically to a glucose molecule to increase the concentration of drug that passes the blood brain barrier (BBB) and increase the concentration of the drug in the brain, and it was additionally complexed physically to a small peptide carrier, which acted as a drug delivery carrier protecting from unwanted reactions/clearance.

The complexation of donepezil into a small peptide carrier (which contained a high number of aromatic amino acids) was quantified by UV-Vis and MRM-MS. A significant amount of donepezil was found to be retained (bound to the peptide) at 1 mg/mL and 5 mg/mL peptide, after centrifugation and washing cycles, which allowed free drug to be removed. Both carriers will be tested in relevant animal models of Alzheimer’s disease to examine if cognition and motor functions can be restored or stabilized.

All interested students and faculty members are invited to attend.