Paclitaxel-loaded polymeric nanoparticles combined with chronomodulated chemotherapy on lung cancer: In vitro and in vivo evaluation

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• 作者：Jie Hu^a ; Shaozhi Fu^a ; Qiuxia Peng^a ; YunWei Han^a ; Jie Xie^b ; Ning Zan^a ; Yue Chen^c ; Juan Fan^a ; ^{fj-joan@163.com}
• 关键词：Paclitaxel (PubChemCID ; 36314) ; Polyethylene glycol (PubChemCID ; 2724259) ; Epsilon-caprolactone (PubChemCID ; 10401) ; Stannous octoate (PubChemCID ; 9318) ; MTT (PubChemCID ; 64965) ; Dimethyl sulfoxide (PubChemCID ; 679) ; Penicillin&ndash ; streptomycin (PubChemCID ; 86591708) ; Acetonitrile (PubChemCID ; 6342) ; Methanol (PubChemCID ; 887) ; EDTA (PubChemCID ; 6049)
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：10 January 2017
• 年：2017
• 卷：516
• 期：1-2
• 页码：313-322
• 全文大小：4720 K
• 卷排序：516

文摘

The objective of our study was to examine the anti-tumor effect of paclitaxel (PTX)-loaded polymeric nanoparticles (PTX-NPs) combined with circadian chronomodulated chemotherapy. Our intention was to screen out the best time of the day for the drug to be administered. PTX-NPs with a diameter of approximately 168 nm were prepared through a thin film dispersion technique. The PTX in PTX-NPs showed an initial fast release subsequently a slower and sustained release. The cytotoxicity of chronomodulated administration of PTX-NPs in vitro confirmed that its cytotoxic effect was lower than that of PTX injection, and showed a time-dependent effect. In addition, anti-tumor effect was examined by analysing tumor growth inhibition rate, micro-vessel density (MVD), cell proliferation and cell apoptosis, following either injection with PTX or administration of PTX-NPs. Micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) was used to evaluate tumor reactivity to PTX-NPs combined with chronomodulated chemotherapy. Taken these results into consideraion, our experiment indicates that PTX-NPs exhibit greater anti-tumor activity against A549 cells, in comparison with PTX injection, and the anti-tumor effect at 15 h after light onset (HALO) administration is the best in all groups. Therefore, prepared PTX-NPs combined with chronomodulated chemotherapy could be a potential treatment for lung cancer.