title: Transferrin receptor-targeted vitamin E TPGS micelles for brain cancer therapy: preparation, characterization and brain distribution in rats.
abstract: The effective treatment of brain cancer is hindered by the poor transport across the blood-brain barrier (BBB) and the low penetration across the blood-tumor barrier (BTB). The objective of this work was to formulate transferrin-conjugated docetaxel (DTX)-loaded d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for targeted brain cancer therapy. The micelles with and without transferrin conjugation were prepared by the solvent casting method and characterized for their particle size, polydispersity, drug encapsulation efficiency, drug loading, in vitro release study and brain distribution study. Particle sizes of prepared micelles were determined at 25 °C by dynamic light scattering technique. The external surface morphology was determined by transmission electron microscopy analysis and atomic force microscopy. The encapsulation efficiency was determined by spectrophotometery. In vitro release studies of micelles and control formulations were carried out by dialysis bag diffusion method. The particle sizes of the non-targeted and targeted micelles were <20 nm. About 85% of drug encapsulation efficiency was achieved with micelles. The drug release from transferrin-conjugated micelles was sustained for >24 h with 50% of drug release. The in vivo results indicated that transferrin-targeted TPGS micelles could be a promising carrier for brain targeting due to nano-sized drug delivery, solubility enhancement and permeability which provided an improved and prolonged brain targeting of DTX in comparison to the non-targeted micelles and marketed formulation.
authors.affiliation: a Department of Pharmacology , Institute of Medical Sciences, Banaras Hindu University , Varanasi , Uttar Pradesh , India .
authors.lastname: Sonali
authors.affiliation: a Department of Pharmacology , Institute of Medical Sciences, Banaras Hindu University , Varanasi , Uttar Pradesh , India .
authors.forename: Poornima
authors.initials: P
authors.lastname: Agrawal
authors.affiliation: a Department of Pharmacology , Institute of Medical Sciences, Banaras Hindu University , Varanasi , Uttar Pradesh , India .
authors.forename: Rahul Pratap
authors.initials: RP
authors.lastname: Singh
authors.affiliation: b Department of Pharmaceutics , PSG College of Pharmacy , Coimbatore , Tamil Nadu , India , and.
authors.forename: Chellappa V
authors.initials: CV
authors.lastname: Rajesh
authors.affiliation: c Department of Pharmaceutics , Indian Institute of Technology, Banaras Hindu University , Varanasi , Uttar Pradesh , India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
authors.affiliation: c Department of Pharmaceutics , Indian Institute of Technology, Banaras Hindu University , Varanasi , Uttar Pradesh , India.
authors.forename: Mahalingam R
authors.initials: MR
authors.lastname: Vijayakumar
authors.affiliation: a Department of Pharmacology , Institute of Medical Sciences, Banaras Hindu University , Varanasi , Uttar Pradesh , India .
authors.forename: Bajrangprasad L
authors.initials: BL
authors.lastname: Pandey
authors.affiliation: a Department of Pharmacology , Institute of Medical Sciences, Banaras Hindu University , Varanasi , Uttar Pradesh , India .
authors.forename: Madaswamy Sona
authors.initials: MS
authors.lastname: Muthu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers; D065546:Drug Liberation; D008823:Micelles; D010316:Particle Size; D051381:Rats; D011990:Receptors, Transferrin / Q000008:administration & dosage* / Q000737:chemistry; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*; D014810:Vitamin E / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011990:Receptors, Transferrin; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel; C014225:tocophersolan
keywords: Brain distribution; brain tumor; cancer nanotechnology; drug release; micelles; vitamin E TPGS