Biodegradable amphiphilic polycaprolactones with enhanced drug loading capacity and their toxicity evaluation through microfluidics
Mihaela C. Stefan, Department of Chemistry and Biochemistry, the University of Texas at Dallas, Richardson, TX 75080 USA.
Amphiphilic polycaprolactone diblock copolymers were synthesized by the ring-opening polymerization of various g-substituted e-caprolactone monomers and self-assembled into the water to form micelles, which can improve the loading of anticancer drugs. The drug-loaded micelles can passively target tumors through enhanced permeability and retention (EPR) effect. Our research has been focused on two strategies to increase the drug loading capacity of the amphiphilic diblock copolymer micelles; a) tuning substituents at the hydrophobic polycaprolactone block, and b) co-loading with polyphenols, such as resveratrol and quercetin, when benzyloxy substituents were employed at the hydrophobic polycaprolactone block. The non-covalent interaction, such as p-stacking and hydrogen bonding interaction between the anticancer drug, doxorubicin, and polyphenol, can increase the drug loading capacity. The co-loading approach can significantly reduce the cardiotoxicity caused by the anticancer drug. Moreover, we created a microfluidic device to cultivate stem cell-derived organoids to simulate the dynamic microenvironment of the organ and test the toxicity of drug-loaded micelles. The cell-cell and cell-matrix interactions found in living organs can improve the evaluation of ex vivo toxicity of drug-loaded micelles.
Bio:
Mihaela C. Stefan received her B.S. in Chemical Engineering and Ph.D. in Chemistry from Politehnica University Bucharest, Romania. She worked as a Postdoctoral Researcher in Matyjaszewski’s group at Carnegie Mellon University from 2002 to 2003. She also worked as a Research Scientist in Richard D. McCullough’s group at Carnegie Mellon University on the synthesis of block copolymers containing semiconducting polythiophenes.
She joined the Department of Chemistry and Biochemistry at the University of Texas at Dallas in 2007, and she is currently a Eugene McDermott Professor and Department Head. She received the NSF Career Award in 2010, the NS&M Outstanding Teacher Award in 2009 and 2017, the Inclusive Teaching Diversity Award in 2012, the President’s Teaching Excellence Award in 2014, Provost’s Award for Faculty Excellence in Undergraduate Research Mentoring in 2015, and Provost’s Award for Faculty Excellence in Graduate Research Mentoring in 2021. She also received the Wilfred T. Doherty Award from the Dallas Forth Worth Local Section of the American Chemical Society in 2021. Her research group is developing novel organic semiconductors for organic electronics, biodegradable and biocompatible polymers for drug delivery applications, and rare novel catalysts for polymerization of dienes and cyclic esters. At the University of Texas at Dallas, she supervised 40 graduate students and 26 Ph.D. students graduated with a Ph.D. in Chemistry under her supervision. She also mentored ~150 undergraduate students who worked in her research lab on various projects.
https://scholar.google.com/citations?user=ibS18zAAAAAJ&hl=en
https://profiles.utdallas.edu/mihaela
https://personal.utdallas.edu/~mci071000/
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