title: Paclitaxel-loaded polymeric nanoparticles combined with chronomodulated chemotherapy on lung cancer: In vitro and in vivo evaluation.
abstract: 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 168nm 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 15h 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.
authors.affiliation: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Shaozhi
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: YunWei
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zan
authors.affiliation: Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: fj-joan@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Fan
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019454:Chronotherapy / Q000379:methods*; D003692:Delayed-Action Preparations; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D000072078:Positron Emission Tomography Computed Tomography; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D011108:Polymers; D017239:Paclitaxel
keywords: Acetonitrile (PubChemCID: 6342); Anti-tumor activity; Chronomodulated chemotherapy; Dimethyl sulfoxide (PubChemCID:679); EDTA (PubChemCID: 6049); Epsilon-caprolactone (PubChemCID:10401); MTT (PubChemCID: 64965); Methanol (PubChemCID: 887); PCL-PEG-PCL; Paclitaxel; Paclitaxel (PubChemCID: 36314); Penicillin–streptomycin (PubChemCID: 86591708); Polyethylene glycol (PubChemCID: 2724259); Polymeric nanoparticles; Stannous octoate (PubChemCID:9318)