TPGS/Poloxamer 407 Nano-Micelle Enhanced the Cytotoxicity of Luteolin on Breast  Cancer Cell Line

Muhammad Redza Fahmi Mod Razif; Kai Bin Liew; Shairyzah Ahmad Hisham; Shamima Abdul Rahman; Siok Yee Chan; Riyanto Teguh Widodo; Yik Ling Chew; Masriana Ling Hassan

Muhammad Redza Fahmi Mod Razif University of Cyberjaya
Kai Bin Liew University of Cyberjaya
Shairyzah Ahmad Hisham University of Cyberjaya
Shamima Abdul Rahman University of Cyberjaya
Siok Yee Chan Universiti Sains Malaysia
Riyanto Teguh Widodo University Malaya
Yik Ling Chew UCSI University
Masriana Ling Hassan Universiti Putra Malaysia

Keywords: Breast Cancer, Cytotoxic Study, Luteolin, Micelle, Poloxamer 407, Vitamin E TPGS

Abstract

Luteolin (Lut) is a flavonoid compound that has been studied widely for its various
anti-cancer properties and sensitization of MDR cells. However, Lut limited solubility and
bioavailability has rendered its potential and clinical use. The combination of this compound
with vitamin E TPGS (TPGS) and poloxamer 407 (Pol) can produce a synergistic effect to
enhance tumor apoptosis and P-glycoprotein inhibition. This study serves to develop an
optimized micelle and investigate the efficacy of luteolin encapsulated in TPGS/Pol micelle in
killing breast cancer cell lines. The micelle was prepared by using film hydration method and
the micellar solution was lyophilized and the cake formed was analyzed. The encapsulation
efficiency was measured by using UV-spectrophotometer and the micellar size was measured
using dynamic light scattering technique. The cytotoxicity of the micellar powder and free
luteolin was measured by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium
Bromide (MTT) assay and breast cancer cell lines MCF-7 and MDA-MB-231 were used. The
optimized micelle was identified to have more than 90% EE with particle size less than 40nm,
in which it came from 10% concentration of surfactants with the ratio of TPGS/Pol: 3:1.
Cytotoxic assay showed enhanced killing of luteolin when encapsulated with TPGS/Pol
micelle on both MCF-7 and MDA-MB-231, compared to free luteolin and blank micelle. This
study has proved that encapsulating hydrophobic drugs with micelle not only increased the
solubility but also increased efficacy in killing breast cancer cells.