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Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes.

ABSTRACT: 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.

SUBMITTER: Cheng Y

PROVIDER: S-EPMC6599616 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes.

Cheng Yilong Y Liu Gary W GW Jain Ritika R Pippin Jeffrey W JW Shankland Stuart J SJ Pun Suzie H SH

ACS biomaterials science & engineering 20181123 12

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 reversibi ...[more]

PMID: 31259236

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