4.7 Article

Ovarian carcinoma biological nanotherapy: Comparison of the advantages and drawbacks of lipid, polymeric, and hybrid nanoparticles for cisplatin delivery

期刊

BIOMEDICINE & PHARMACOTHERAPY
卷 109, 期 -, 页码 475-483

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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.10.158

关键词

Ovarian cancer; Lipid nanoparticles; Polymeric nanoparticles; Lipid-polymer hybrid nanoparticles; Cisplatin

资金

  1. Zhejiang Medical and Health Science and Technology Project [2014KYA010]
  2. Clinical study on the protection of ovarian function by GnRH-a during chemotherapy for malignant ovarian germ cell tumors [2014/06-2017/06]

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Ovarian carcinoma is one of the most common cancers among women. The most common type of ovarian cancer is epithelial ovarian cancer and cisplatin (DDP) is one of the most interesting chemotherapeutic drugs in clinical regimens for ovarian cancer. Nanoparticles (NPs) including lipid NPs, polymeric NPs, liposomes, dendrimers, oligomers, and nanotubes were usually used for anti-cancer drug delivery. In this study, DDP loaded nanostructured lipid carriers (DDP-NLC), polymeric NPs (DDP-PNP), and lipid-polymer hybrid nanoparticles (DDPLPN) were prepared for the evaluation in vitro and in vivo. The efficiency of these three kinds of the NPs was compared in terms of in vitro drug release, cellular uptake, in vitro cell growth inhibition, in vivo pharmacokinetics, biodistribution and in vivo antitumor in mice. The size of DDP-PNP (119.8 nm) was smaller than DDP-NLC (132.4 nm) and DDP-LPN (141.2 nm). The release of DDP from DDP-NLC was faster than DDP-PNP. Cellular uptake efficiency of DDP-NLC and DDP-LPN was significantly higher than DDP-PNP. In vivo pharmacokinetics evaluation showed that plasma concentration -time curves (AUCs) of DDP-NLC, DDP-PNP, DDP-LPN and free DDP are 128, 210, 247, and 16 mg/L h, with T-1/2 of 4.4, 5.1, 5.5, and 1.7 mg/L h. DDP-LPN exhibits the highest AUC and the longest T-1/2. In vivo antitumor efficacy results investigated on ovarian cancer bearing BALB/c mice model demonstrated that DDP-LPN showed the strongest antitumor effect. In vitro and in vivo studies demonstrated that DDP-NLC, DDP-PNP and DDP-LPN have different advantages due to the various evaluations. The in vivo anti-tumor results indicate that DDP-LPN may have the best tumor inhibition ability. DDP-NLC, DDP-PNP, and DDP-LPN developed in this study could be used as promising strategies for the treatment of ovarian cancer according to different demands.

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