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Gastric cancer combination therapy: synthesis of a hyaluronic acid and cisplatin containing lipid prodrug coloaded with sorafenib in a nanoparticulate system to exhibit enhanced anticancer efficacy and reduced toxicity

Authors Yang F, Li A, Liu H, Zhang H

Received 11 June 2018

Accepted for publication 1 September 2018

Published 4 October 2018 Volume 2018:12 Pages 3321—3333

DOI https://doi.org/10.2147/DDDT.S176879

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Manfred Ogris


Feng Yang,1 Aimei Li,2 Han Liu,3 Hairong Zhang1

1Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of South China, Hengyang 421000, Hunan, People’s Republic of China

Purpose: Gastric cancer is one of the most common human epithelial malignancies, and using nanoparticles (NPs) in the diagnosis and treatment of cancer has been extensively studied. The aim of this study was to develop hyaluronic acid (HA) containing lipid NPs coloaded with cisplatin (CDDP) and sorafenib (SRF) for the treatment of gastric cancer.
Materials and methods: HA and CDDP containing lipid prodrug was synthesized using polyethylene glycol (PEG) as a linker (HA-PEG-CDDP). HA-PEG-CDDP and SRF were entrapped into the lipid NPs by nanoprecipitation method (H-CS-NPs). The physicochemical and biochemical properties such as size, zeta potential, and drug release pattern were studied. In vitro viability was also evaluated with MKN28 and SGC7901 human gastric cancer cells. In vivo testing including biodistribution and accumulation in tumor tissue was applied in gastric tumor-bearing mice to confirm the inhibition of gastric cancer.
Results: H-CS-NP has a particle size of 173.2±5.9 nm, with a zeta potential of -21.5±3.2 mV. At day 21 of in vivo treatment, H-CS-NPs inhibited the tumor volume from 1,532.5±41.3 mm3 to 259.6±16.3 mm3 with no obvious body weight loss. In contrast, mice treated with free drugs had body weight loss from 20 to 15 g at the end of study.
Conclusion: The results indicate that H-CS-NPs enhanced the antitumor effect of drugs and reduced the systemic toxicity effects. It could be used as a promising nanomedicine for gastric cancer combination therapy.

Keywords:
nanocarriers, chemotherapy, polyethylene glycol, enhanced permeability and retention effect, reticuloendothelial system

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