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.

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-&alpha;-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

“…[47][48][49] TPGS possesses a lipophilic nonpolar head and a hydrophilic tail and would be an ideal surface-active agent to provide a high drug emulsification effect. 50,51 It has been reported that a self-assembled mixture of micelles (TPGS-Icariside IIphospholipid complex) successfully improved the solubility of Icariside II and alleviated efflux in Caco-2 cells. 10 As a pluronic excipient, P105 is a well-known polymeric inhibitor of P-gp and functions via inhibiting ATPase and fluidizing membrane.…”

Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor

“…Few similar recent important investigations (Hao et al, 2015, Sonali et al, 2016b, Sonali et al, 2016c) also developed nanoformulations with receptor targeting agents. However, they were constituted with absolutely different constituents such as D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS), poly-lactic-co-glycolic acid (PLGA).…”

“…However, they were constituted with absolutely different constituents such as D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS), poly-lactic-co-glycolic acid (PLGA). Further, Sonali et al (2016c) developed micelles. Hao et al (2015) developed multifunctional nanoparticles and Sonali et al (2016b) developed theranostic liposomes.…”

“…In this context colloidal drug carrier especially nanoliposomes have gained significant interest among the researchers around the globe. (Jain, 2012;Zhang & Zhang, 2013;Hao et al, 2015;Sonali et al, 2016a;Sonali et al, 2016b;Sonali et al, 2016c).…”

Novel carvedilol paediatric nanomicelle formulation: in-vitro characterization and in-vivo evaluation

“…It is a commercially available biomaterial which has been approved by the FDA as a generally regarded as safe (GRAS)‐listed oral supplement. Due to its amphiphilic nature, TPGS micelles (alone or mixed with other biomaterials) have been developed to encapsulate hydrophobic drugs …”