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

ABSTRACT: Chemotherapy 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.

SUBMITTER: Zhao X

PROVIDER: S-EPMC6804453 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Zhao Xiyue X Liu Xiaoyu X Zhang Pengcheng P Liu Yiran Y Ran Wei W Cai Ying Y Wang Junyang J Zhai Yihui Y Wang Guanru G Ding Yaping Y Li Yaping Y

Acta pharmaceutica Sinica. B 20190614 5

Chemotherapy 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 C<sub>16</sub>-GNNQQNYKD-OH-based nan ...[more]

PMID: 31649853

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Project description:BackgroundRheumatoid arthritis (RA) tends to occur in symmetrical joints and is always accompanied by synovial hyperplasia and cartilage damage. Triptolide (TP), an extract from Tripterygium, has anti-inflammatory and immunomodulatory properties and could be used in the treatment of RA. However, its poor water solubility and the multi-system lesions caused by the use of this substance limit its clinical application. Therefore, it would be of great significance to assemble a composite nanoparticle hydrogel and apply it to a collagen-induced arthritis (CIA) mouse model to investigate the therapeutic effect and biosafety of this compound.MethodTP@HSA nanoparticles (TP@HSA NPs) were fabricated with a self-assembly method; a thermosensitive hydrogel loaded with the TP@HSA NPs (TP@HSA NP hydrogel) was prepared by using chitosan and beta- glycerophosphate (β-GP) and was then intra-articularly injected into CIA mice. The changes in joint swelling were measured with a digital caliper, and inflammation and cartilage damage were evaluated by using hematoxylin and eosin (H&E) and safranin O-fast green (SO&FG) staining, respectively.ResultsTP@HSA NPs with an average diameter of 112 ± 2 nm were successfully assembled, and their encapsulation efficiency and drug loading efficiency were 47.6 ± 1.5% and 10.6 ± 3.3%, respectively. The TP@HSA NP hydrogel had a gelation temperature of 30.5 ± 0.2 °C, which allows for its injection at low temperatures and its sol-gel transformation under physiological conditions within 2 min, making it a suitable drug depot. The TP@HSA NP hydrogel was intra-articularly injected into CIA mice; it released TP locally and exerted anti-inflammatory and immunomodulatory effects, alleviating synovial inflammation and cartilage damage effectively.ConclusionsWe successfully fabricated a TP@HSA NP-loaded thermosensitive hydrogel with good biosafety, which can release TP slowly for the treatment of RA. Our study provides a basis for the development of TP-based innovative preparations and has good application prospects.

Dataset Information

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

Publications

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

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