title: Vitamin E TPGS conjugated carbon nanotubes improved efficacy of docetaxel with safety for lung cancer treatment.
abstract: The aim of this work was to develop multi-walled carbon nanotubes (MWCNT), which were coated or covalently conjugated with d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), and loaded docetaxel as a model drug for effective treatment to lung cancer in comparison with the commercial docetaxel injection (Docel™). The human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) study of the docetaxel/coumarin-6 loaded MWCNT. The safety of MWCNT formulations were studied by the measurements of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the TPGS conjugated MWCNT could be 80 folds more effective than Docel™ after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells were appeared significantly (P<0.05) in the sub G1 phase for TPGS conjugated MWCNT. Results of TPGS conjugated MWCNT have showed better efficacy with safety than non-coated or TPGS coated MWCNT and Docel™.
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Rahul Pratap
authors.initials: RP
authors.lastname: Singh
authors.affiliation: Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.lastname: Sonali
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Bajarangprasad L
authors.initials: BL
authors.lastname: Pandey
authors.affiliation: Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address: kochbiplob@gmail.com.
authors.forename: Biplob
authors.initials: B
authors.lastname: Koch
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005, India; Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. Electronic address: muthubits@rediffmail.com.
authors.forename: Madaswamy S
authors.initials: MS
authors.lastname: Muthu
mesh_terms: D000072283:A549 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003374:Coumarins / Q000737:chemistry; D000077143:Docetaxel; D065546:Drug Liberation; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D020099:Coated Materials, Biocompatible; D003374:Coumarins; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D043823:Taxoids; D013844:Thiazoles; C517282:coumarin 6; D014810:Vitamin E; D000077143:Docetaxel; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; C014225:tocophersolan
keywords: Lung cancer; MWCNT; Nanomedicine; Nanotechnology; ROS level; Safety; TPGS conjugation