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.

• Brain distribution
• brain tumor
• cancer nanotechnology
• drug release
• micelles
• vitamin E TPGS

Acknowledgements

M.S. Muthu acknowledges the Science & Engineering Research Board (SERB), New Delhi, India for a research project under Fast track scheme for young scientists (OYS). Project file number is SR/FT/LS-132/2011. We acknowledge Interdisciplinary School of Life Sciences (ISLS), Faculty of Science, Banaras Hindu University, Varanasi, India, for doing HPLC analysis of samples. We also acknowledge Electron Microscopy Facility, Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India, in carrying out TEM analysis of samples.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.