Shi Yuqiong, Liu Wei, Wu Xiangrong, Zhu Jinhua, Zhou Danyang, Liu Xiuhua
Henan International Joint Laboratory of Medicinal Plants Utilization, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China.
Nanomaterials (Basel). 2021 Oct 26;11(11):2854. doi: 10.3390/nano11112854.
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.
羟基喜树碱（HCPT）较差的水溶性和严重的副作用限制了其临床应用；因此，有必要合成具有良好溶解性的适用纳米药物载体，以拓展HCPT的应用。在本研究中，首先合成并表征了一种以两性羧酸配体作为连接体的亲水性金属有机框架（MOF）。然后，将水溶性丙烯酰胺和甲基丙烯酸用作单体，制备出溶解度为370 μg/mL的水溶性聚酸聚合物MOF@P。研究了MOF@P材料对HCPT负载量和溶解度的影响。结果表明，该聚合物材料可提高HCPT在水中的溶解度。此外，体外释放研究表明，MOF@P聚合物复合材料对HCPT具有缓释作用，在pH 7.4条件下72 h内的累积释放率为30.18%。此外，细胞毒性试验表明亲水性MOF和MOF@P具有较低的细胞毒性。结果表明，所制备的MOF@P聚合物复合物可用于临床HCPT的缓释。
