title: Bioadhesive micelles of d-α-tocopherol polyethylene glycol succinate 1000: Synergism of chitosan and transferrin in targeted drug delivery.
abstract: The aim of this work was to prepare targeted bioadhesive d-α- tocopheryl glycol succinate 1000 (TPGS) micelles containing docetaxel (DTX) for brain targeted cancer therapy. Considering the unique bioadhesive feature of chitosan, herein, we have developed a synergistic transferrin receptor targeted bioadhesive micelles using TPGS conjugated chitosan (TPGS-chitosan), which target the overexpressed transferrin receptors of glioma cells for brain cancer therapy. The micelles were prepared by the solvent casting method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release. The IC50values demonstrated transferrin receptor targeted TPGS-chitosan micelles could be 248 folds more effective than Docel™ after 24h treatment with the C6 glioma cells. Further, time dependent bioadhesive cellular uptake study indicated that a synergistic effect was achieved with the chitosan and transferrin in targeted TPGS-chitosan micelles through the biodhesive property of chitosan as well as transferrin receptor mediated endocytosis. The in-vivo pharmacokinetic results demonstrated that relative bioavailability of non-targeted and targeted micelles were 2.89 and 4.08 times more effective than Docel™ after 48h of treatments, respectively.
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.lastname: Sonali
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 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 Pharmaceutics, PSG College of Pharmacy, Peelamedu, Coimbatore 641004, India.
authors.forename: Chellapa V
authors.initials: CV
authors.lastname: Rajesh
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: D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry*; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D008823:Micelles; D014168:Transferrin; D011092:Polyethylene Glycols; D048271:Chitosan; D024502:alpha-Tocopherol; C000595209:polyethylene glycol 1000
keywords: Bioadhesive study; Brain cancer; Chitosan; Synergistic effect; TPGS; Targeted nanomedicines