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Boronic Acid Copolymers for Direct Loading and Acid-Triggered Release of Bis-T-23 in Cultured Podocytes

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posted on 23.11.2018 by Yilong Cheng, Gary W. Liu, Ritika Jain, Jeffrey W. Pippin, Stuart J. Shankland, Suzie H. Pun
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.

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