Boronic Acid Copolymers for Direct Loading and Acid-Triggered Release of Bis-T-23 in Cultured Podocytes
journal contributionposted on 23.11.2018 by Yilong Cheng, Gary W. Liu, Ritika Jain, Jeffrey W. Pippin, Stuart J. Shankland, Suzie H. Pun
Any type of content formally published in an academic journal, usually following a peer-review process.
We report an acid-reversible linker for triggered release of Bis-T-23, an experimental small molecule drug for kidney disease treatment that restores podocyte morphology during disease. Bis-T-23 contains catechols, which form an acid-reversible, covalent boronate ester bond with boronic acids. We synthesized phenylboronic acid-containing polymers using reversible addition–fragmentation chain transfer polymerization that were able to directly load and solubilize Bis-T-23. Because of the reversibility of the boronic ester bond, drug was released in its native form in a pH-dependent manner. The polymers rapidly trafficked into acidic compartments and did not exhibit cytotoxicity, and polymer-drug conjugates successfully delivered Bis-T-23 into cultured podocytes.