Gambogic acid-loaded PEG–PCL nanoparticles act as an effective antitumor agent against gastric cancer. (2nd January 2018)

• Record Type: Journal Article
• Authors: Zhang, Dinghu; Zou, Zhengyun; Ren, Wei; Qian, Hanqing; Cheng, Qianfeng; Ji, Liulian; Liu, Baorui; Liu, Qin
• Is Part Of: Pharmaceutical development and technology. Volume 23:Number 1(2018)
• Page Start: 33
• Page End: 40
• Publication Date: 2018-01-02
• Subjects: Anticancer -- peritumor -- nanoparticles -- drug delivery; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.1080/10837450.2017.1295068
• Languages: English
• ISSNs: 1083-7450

Abstract

Abstract: Poor water solubility and side effects hampered the clinical application of gambogic acid (GA) in cancer therapy. Accordingly, GA-loaded polyethylene glycol-poly(ɛ-caprolactone) (PEG–PCL) nanoparticles (GA-NPs) were developed and administered peritumorally to evaluate their antitumor activity. The particle size, polydispersity index, encapsulation efficiency and loading capacity of GA-NPs were 143.78 ± 0.054 nm, 0.179 ± 0.004, 81.3 ± 2.5% and 14.8 ± 0.6%, respectively. In addition, GA-NPs showed excellent stability, good biocompatibility and sustained release profile. Endocytosis studies in vitro demonstrated that the GA-NPs were effectively taken up by tumor cells in a time-dependent manner. In vivo real-time imaging showed that the nanoparticles effectively accumulated within the tumor tissue after peritumoral administration. The cytotoxicity study revealed that the GA-NPs effectively inhibited the proliferation of gastric cancer cells . In vivo antitumor therapy with peritumoral injection of GA-NPs exhibited superior antitumor activity compared with free GA. Moreover, no toxicity was detected in any treatment group. Histological studies confirmed a lower cell density and a higher number of apoptotic cells in the GA-NPs group compared with the free GA group. Furthermore, the expression level of the cysteine proteases 3 precursor (pro-caspase3), a crucial component of cellular apoptotic pathways, was efficiently reduced in mice treated with GA-NPs. In conclusion, the GA-NPs system provided an efficient drug delivery platform for chemotherapy.