Titania Nanoparticles for the Intracellular Delivery of Paclitaxel in Breast Cancers

Abstract

The limitation in broad spectrum of anticancer activity of Paclitaxel (PCT) in clinical application is due to its serious side effects. Therefore, the task of the present study was to prepare a novel “smart” pH-responsive drug delivery system (DDS) with the use of titanium dioxide (TiO2) nanoparticles as a vehicle. In addition, TiO2 would act as a controlled release formulation for PCT with higher therapeutic efficiency. TiO2 nanopowders were synthesized by high temperature hydrolysis of TiOSO4 aqueous solution and then extensive characterization like DLS, NTA, TEM, XRD FT-IR and zeta potential had been performed so as to find its suitability as a drug delivery vehicle. PCT-TiO2 nanocomposites were prepared by loading PCT over TiO2 nanoparticles with the formation of complexes through transition metal titanium. The quantitative estimation of amount of drug release, as verified through HPLC showed maximum release of 87.197 µg at pH 5.2, 70.023 µg at pH 6.0 and minimum release of 20.341 µg at pH 7.4. The targeted drug delivery has been established with the rapid release of PCT at pH 5.0 and 6.0 rather than at pH 7.4. In order to understand the mechanism, a proposed model system accomplishing the role of extracellular concentration of Ca+2 during drug release has been given. The improved anticancer activity of PCT-TiO2 nanocomposites and its time dependent uptake property has been demonstrated by flow cytometry analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and 4′,6-diamidino- 2-phenylindole (nuclear staining). In MCF-7 breast cancer cell line, the nanocomposites has triggered the increase in intracellular concentration of PCT with enhanced anticancer efficiency by inducing apoptosis as observed through flow cytometry study. Hence its efficiency as a DDS towards breast cancer cell line has been achieved. The outcomes of the study clearly suggest a “smart” PCT delivery strategy and hence serve as a promising approach in cancer therapy.