Graduate Research Assistant- Ph.D. Candidate University of Maryland Baltimore Baltimore, Maryland
Leukemias are devastating blood cancers that affect all ages. A two-carbon-linked dimeric artemisinin analog (ART631) is a potent anti-leukemic drug at nanomolar concentrations but has limiting water-solubility. Additionally, clinical artemisinin analogs have short in vivo half-lives that require frequent dosing to maintain pharmacologically active plasma concentrations. Here, we created a novel platform nanotechnology to increase the water solubility >400-fold of ART631 via UV emulsion polymerization and sustain the release of ART631 for at least one month. ART631-loaded biodegradable nanogels (NanoART631) had IC50 < 40nM against MOLM14, MV4;11, and THP1 cells, and were not toxic to two nonmalignant cell lines up to at least 1mg/mL. The single-dose IV maximal tolerated dose (MTD) of NanoART631 in NRG mice was 500mg/kg. Completion of the project will lead to a paradigm shift innovative technology to significantly increase the water solubility of hydrophobic drugs and an effective long-term therapy to treat leukemias and other diseases.
Learning Objectives:
Upon completion, participant will be able to learn an innovative platform technology that improves water solubility of hydrophobic drugs hundreds of folds.
Upon completion, participant will be able to learn about developing new nanotechnology for sustained released of artemisinin derivatives to effectively treat leukemia.
Upon completion, participant will be able to learn about using NMR to quantify drug loading content, encapsulation efficiency, and release percent.