Anti-tumor efficacy of folate modified PLGA-based nanoparticles for the co-delivery of drugs in ovarian cancer
Authors Li S, Li X, Ding J, Han L, Guo X
Received 21 November 2018
Accepted for publication 14 March 2019
Published 18 April 2019 Volume 2019:13 Pages 1271—1280
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Cristiana Tanase
Shu Li, Xiaofeng Li, Jianyi Ding, Lingfei Han, Xiaoqing Guo
Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
Background: Ovarian cancer is a leading cause of death in gynecologic malignancies. The high mortality is mainly caused by advanced stage at presentation in most patients. Even after the combination of cytoreductive surgery and systemic platinum and taxane treatment, most patients relapse and eventually succumb to the disease. Therefore, there is an urgent need for new treatments.
Purpose: A novel folate (FA)-targeted co-delivery of docetaxel (DTX) and gemcitabine (GEM) nanoparticles (NPs) was developed to overcome ovarian cancer.
Materials and methods: Physicochemical characteristics of NPs such as size, morphology, and release profiles were explored. In vitro and in vivo studies were carried out to assess the efficacy of their antitumor activity in target cells.
Results: FA modified DTX and GEM co-loaded NPs were prepared using the solvent evaporation method. The NPs with a particle size of ∼120nm were stable in the observation period. The hemolysis results indicated that FA-PEG2000-PLGA was potentially feasible for targeted antitumor drug delivery through blood circulation. In vitro release study suggested that in comparison with the free drug, PLGA-DTX/GEM NPs and FA-PEG2000-PLGA-DTX/GEM NPs had sustained-release properties. However, there was no obvious difference between the two NPs with the same drug in the release profile. Ovarian cancer cells in vitro efficiently took up the non-targeted and FA-targeted NPs; improved cytotoxicity was observed in the FA-targeted NPs, showing a 3.59- fold drop in the IC50 in SKOV-3 cells as compared to DTX/GEM alone. Cellular uptake showed that through surface modification, more drugs entered the cell successfully. Pharmacodynamics results showed a statistically significant effect on the rate of reduction of tumor volume for FA-PEG2000-PLGA-DTX/GEM NPs than other groups and no toxicity of organs.
Conclusion: The present study indicates that the FA-PEG2000-PLGA-DTX/GEM NPs provides a promising platform for the treatment of ovarian cancer.
Keywords: folate, co-delivery, docetaxel, gemcitabine, nanoparticles
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