A Water-Soluble Polyacid Polymer Based on Hydrophilic Metal–Organic Frameworks Using Amphoteric Carboxylic Acid Ligands as Linkers for Hydroxycamptothecin Loading and Release In Vitro

Abstract

The poor water solubility and severe side effects of hydroxycamptothecin (HCPT) limit its clinical application; therefore, it is necessary to synthesize applicable nanodrug carriers with good solubility to expand the applications of HCPT. In this study, a hydrophilic metal–organic framework (MOF) with amphoteric carboxylic acid ligands as linkers was first synthesized and characterized. Then, water-soluble acrylamide and methacrylic acid were applied as monomers to prepare a water-soluble polyacid polymer MOF@P, which had a solubility of 370 μg/mL. The effects of the MOF@P material on the HCPT loading and solubility were investigated. The results showed that the polymer material could improve the HCPT solubility in water. Moreover, the in vitro release study indicated that the MOF@P polymeric composite exhibited a sustained-release effect on HCPT, with a cumulative release rate of 30.18% in 72 h at pH 7.4. Furthermore, the cytotoxicity test demonstrated that the hydrophilic MOF and the MOF@P had low cell toxicities. The results indicate that the prepared MOF@P polymeric complex can be applied for the sustained release of HCPT in clinics.

Keywords

• polyacid polymer
• metal organic frameworks
• HCPT delivery