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Layer-by-layer nanoparticles co-loading gemcitabine and platinum (IV) prodrugs for synergistic combination therapy of lung cancer

Authors Zhang R, Ru Y, Gao Y, Li J, Mao S

Received 1 June 2017

Accepted for publication 2 August 2017

Published 5 September 2017 Volume 2017:11 Pages 2631—2642

DOI https://doi.org/10.2147/DDDT.S143047

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 3

Editor who approved publication: Dr Sukesh Voruganti

Rongrong Zhang, Yun Ru, Yiping Gao, Jinyin Li, Shilong Mao

Department of Pharmacy, Shanghai Xuhui District Central Hospital, Zhongshan Hospital Affiliated to Fudan University Xuhui Hospital, Shanghai, People’s Republic of China

Purpose: Cisplatin plus gemcitabine (GEM) is a standard regimen for the first-line treatment of advanced non-small cell lung cancer. The aim of this study was to prepare biocompatible and biodegradable polymeric prodrugs and construct nanoparticles (NPs) with layer-by-layer (LbL) technique.
Methods: Platinum (Pt) (IV) complex with a carboxyl group was conjugated to the amino group of chitosan (CH), resulting in a CH-Pt conjugation with positive charge. GEM with amino group was conjugated to the carboxyl group of hyaluronic acid (HA), resulting in a HA-GEM conjugation with negative charge. Novel LbL NPs consisting of the CH-Pt core and the HA-GEM layer, named as HA-GEM/CH-Pt NPs, were constructed. The physicochemical properties of the HA-GEM/CH-Pt NPs were investigated. In vitro cytotoxicity against human non-small lung cancer cells (NCl-H460 cells) was investigated, and in vivo antitumor efficiency was evaluated on mice bearing NCl-H460 cells xenografts.
Results: HA-GEM/CH-Pt NPs have a size of about 187 nm, a zeta potential value of -21 mV and high drug encapsulation efficiency of 90%. The drug release of HA-GEM/CH-Pt NPs exhibited a sustained behavior. HA-GEM/CH-Pt NPs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against lung cancer animal model compared to the single-drug-loaded NPs and free drug solutions.
Conclusion: The results demonstrated that the HA-GEM/CH-Pt NPs might be a promising system for the synergetic treatment of lung carcinoma.

Keywords: lung cancer, combination chemotherapy, cisplatin, gemcitabine, layer-by-layer technology

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