Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma

Publication date: Available online 14 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xiyue Zhao, Xiaoyu Liu, Pengcheng Zhang, Yiran Liu, Wei Ran, Ying Cai, Junyang Wang, Yihui Zhai, Guanru Wang, Yaping Ding, Yaping LiAbstractChemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7±0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.Graphical abstractC16-N hydrogel containing triptolide was created as an intraperitoneal depot for the treatm...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research