期刊
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
卷 66, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jddst.2021.102782
关键词
Curcumol; HepG2 cells; PEG-PCL polymersome; Growth inhibition; Apoptosis
资金
- Department of Science & Technology of Liaoning province
- Liaoning Provincial Department of Education Project ' Construction of Novel Biomimetic Targeted Polymeric Micelle Drug Delivery System and Its Antitumor Research '
The study synthesized a curcumol derivative CD-2e with improved bioavailability for treating liver cancer. CD-2e showed enhanced inhibition of cell proliferation and induction of apoptosis in HepG2 cells compared to curcumol, along with cell cycle arrest in S phase. Additionally, the study developed PEG-PCL-CD-2e polymersomes for improved drug delivery, which demonstrated rapid release of CD-2e and enhanced pharmacokinetic properties compared to free CD-2e.
Curcumol is a natural plant product with anti-tumor properties. However, the clinical application of curcumol is limited by its low water solubility. In this study, we synthesized a curcumol derivative 2e (CD-2e) with improved bioavailability and evaluated its cell growth-regulating activities in human hepatoma HepG2 cells, a liver cancer precursor cell line. Using the clone formation assay, we detected that CD-2e inhibits proliferation and activity of HepG2 cells more effectively than curcumol. Flow cytometry analysis indicated that CD-2e can induce HepG2 cell apoptosis and arrests cell cycle in S phase. Acridine orange-ethidium bromide(AO-EB) double staining indicated that CD-2e triggers HepG2 cell apoptosis in a time-dependent manner. Additionally protein expression analysis showed that CD-2e treatment reduced expression levels of c-Jun N-terminal kinase 1 (JNK1) and its phosphorylated form, P-JNK1. PEG-PCL polymersome carrying CD-2e (PEG-PCL-CD-2e) were generated to improve drug delivery. The prepared PEG-PCL-CD-2e had a uniform particle size distribution, with an average particle size of about 190 nm, and good in vitro stability. The drug release and cell uptake experiments showed that PEG-PCL-CD-2e can rapidly release CD-2e in a weak-acid environment in vitro. Pharmacokinetic studies indicated that, compared with free CD-2e, PEG-PCL-CD-2e enhanced Cmax and Area Under Curve (AUC) (0-infinity) by about 1.93-fold and 2.45-fold. The T1/2 was prolonged to 2.59 +/- 0.03 h.
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