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.

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).