mp6b01008_si_001.pdf (1.85 MB)
Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia
journal contribution
posted on 2017-01-31, 00:00 authored by Robert
C. Deller, Paraskevi Diamanti, Gabriella Morrison, James Reilly, Benjamin C. Ede, Robert Richardson, Kristian Le Vay, Andrew M. Collins, Allison Blair, Adam W. PerrimanThe
chemotherapeutic Parthenolide is an exciting new candidate
for the treatment of acute lymphoblastic leukemia, but like many other
small-molecule drugs, it has low aqueous solubility. As a consequence,
Parthenolide can only be administered clinically in the presence of
harmful cosolvents. Accordingly, we describe the synthesis, characterization,
and testing of a range of biocompatible triblock copolymer micelles
as particle-based delivery vectors for the hydrophobic drug Parthenolide.
The drug-loaded particles are produced via an emulsion-to-micelle
transition method, and the effects of introducing anionic and cationic
surface charges on stability, drug sequestration, biocompatibility,
and efficacy are investigated. Significantly, we demonstrate high
levels of efficacy in the organic solvent-free systems against human
mesenchymal stem cells and primary T-acute lymphoblastic leukemia
patient cells, highlighting the effectiveness of the delivery vectors
for the treatment of acute lymphoblastic leukemia.