title: TPGS-chitosan cross-linked targeted nanoparticles for effective brain cancer therapy.
abstract: Brain cancer, up-regulated with transferrin receptor led to concept of transferrin receptor targeted anticancer therapeutics. Docetaxel loaded d-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-chitosan) nanoparticles were prepared with or without transferrin decoration. In vitro experiments using C6 glioma cells showed that docetaxel loaded chitosan nanoparticles, non-targeted and transferrin receptor targeted TPGS-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity. The IC50values of non-targeted and transferrin receptor targeted nanoparticles from cytotoxic assay were found to be 27 and 148 folds, respectively higher than Docel™. In vivo pharmacokinetic study showed 3.23 and 4.10 folds enhancement in relative bioavailability of docetaxel for non-targeted and transferrin receptor targeted nanoparticles, respectively than Docel™. The results have demonstrated that transferrin receptor targeted nanoparticles could enhance the cellular internalization and cytotoxicity of docetaxel via transferrin receptor with improved pharmacokinetics for clinical applications.
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Poornima
authors.initials: P
authors.lastname: Agrawal
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: 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: Laksmi
authors.initials: L
authors.lastname: Kumari
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: 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, PSG College of Pharmacy, Peelamedu, Coimbatore 641004, India.
authors.forename: Chellapa V
authors.initials: CV
authors.lastname: Rajesh
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005, India.
authors.forename: Abhishesh K
authors.initials: AK
authors.lastname: Mehata
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 Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Bajarangprasad L
authors.initials: BL
authors.lastname: Pandey
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: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D000077143:Docetaxel; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D043823:Taxoids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D011990:Receptors, Transferrin; D043823:Taxoids; D000077143:Docetaxel; D048271:Chitosan; D024502:alpha-Tocopherol
keywords: Brain cancer; Chitosan; Synergistic effect; TPGS; Targeted nanomedicines; Transferrin receptor