1. Nano-engineered titanium wires as drug-eluting
implants for human breast cancer therapy
Mima Kurian1,2, Karan Gulati1, Moom Sinn Aw1, Shelley Hay3, Andreas Evdokiou3, Dusan Losic1
1 School of Chemical Engineering, University of Adelaide, SA
2 Amity Institute of Nanotechnology, Amity University, Uttar Pradesh, India
3 Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville, SA
METHODOLOGY
(a) Fabrication of TNT/Ti wires
Annealed Ti wires (0.5 mm diameter, 10mm length) were polished mechanically and
electrochemically prior to anodization. Electrochemical anodization was performed at a
constant voltage of 75 V for 30 min in ammonium fluoride/ethylene glycol electrolyte [3].
(b) Drug loading and in-vitro drug release studies
Drug loading was performed as described in [4] and the in-vitro drug release was
performed in phosphate buffered saline (pH 7.2) using UV-Visible spectrophotometry.
Total DOX loaded was calculated as a measure of the total drug released from TNT/Ti.
(c) In-vitro cell viability studies
In-vitro studies were performed to study the effect of TNT/Ti-DOX wires on MDA-MB-
231-TXSA cells used as the model breast cancer cell lines.
(d) Preliminary ex-vivo analysis
Ex-vivo mammary fat pad tumors excised from mouse and grown on collagen sponges
were implanted with single TNT/Ti-DOX wire; to investigate the effects of DOX loaded
wires on breast cancer tissues.
REFERENCES
[1] Boyle P, Levin B. World cancer report 2008: IARC Press, International Agency for Research on Cancer; 2008.
[2] Skeel RT, Khleif S. Handbook of cancer chemotherapy: Lippincott Williams & Wilkins; 2011.
[3] Gulati K, Aw MS, Losic D. Drug-eluting Ti wires with titania nanotube arrays for bone fixation and reduced bone infection.
Nanoscale research letters. 2011;6(1):1-6.
[4] Aw MS, Gulati K, Losic D. Controlling drug release from titania nanotube arrays using polymer nanocarriers and
biopolymer coating. Journal of Biomaterials and Nanobiotechnology. 2011;2(5):477-84
ACKNOWLEDGEMENTS
Figure 1. Schematic representation of the fabrication of titania nanotubes (TNTs) on Ti wire
and the proposed drug-eluting implant for localized antitumor activity.
DOX = Doxorubicin
RESULTS AND DISCUSSION
Figure 2. A) SEM images of TNT/Ti wires prepared by electrochemical anodization of Ti wire,
(B) top view of nanotube structures, (C) cross-sectional & bottom view of TNT showing highly
ordered and uniform nanotubes (30 nm in diameter, 15 µm in length) with closed bottom
In-vitro drug release studies
Figure 3. In-vitro
release profile of DOX
Effects of DOX -TNT/Ti wires on MDA-MB-231-TXSA cells (in-vitro)
Figure 4. In-vitro studies on cultured cancer cells within 48 h incubation
Preliminary ex-vivo analysis on human breast cancer tissue
CONCLUSIONS
 Self-ordered TNTs were fabricated on Ti wire, and successfully loaded with 33 mg
DOX
 Slow sustained in-vitro release of DOX from TNTs lasted 7 days
 Cells adhering to the DOX loaded TNT/Ti wires do not interfere with DOX elution rate
and pattern
 Unloaded TNT/Ti wires caused no cell death on cancer cells
 No bacterial infection observed in any of the cultures (in-vitro and ex-vivo)
indicating sterility of TNT/Ti wires fabricated
 Infiltration of DOX from TNT/Ti wires into the tumor tissues (ex-vivo) showed
effective cell death near its vicinity and potential to be used as implants for
localized chemotherapy
Structural characterization of TNT/Ti wires
Authors acknowledges the financial support of the Australian Research Council (DP 120
101 680), The University of Adelaide and The Basil Hetzel Institute.
Figure 5. Ex-vivo mammary fat pad tumours incubated with unloaded and DOX loaded
TNT/Ti wire implants for 4 days, showing diffusion of drug from wire into tumour tissue
INTRODUCTION
Statistics show that there are at present, nearly a million women worldwide
suffering from breast cancer [1]. Current treatments including chemo/radiotherapy
often cause high cytotoxicity to normal cells, have low bioavailability and require
multiple dosing, resulting in numerous side effects, e.g. immuno-suppression [2].
Local therapies with the aid of implants is recognized as a more advantageous
approach over systemic ones under these conditions, due to their high selectivity &
thus effective in situ drug delivery.
We hereby propose titania nanotubes (TNTs) fabricated on titanium wires
as drug-eluting implants for localized anti-cancer therapy to combat
breast cancer.
Anti-cancer drug doxorubicin hydrochloride (DOX) was loaded into TNTs on Ti wires;
followed by release from TNT/Ti wires monitored in-vitro and ex-vivo on breast
cancer tissue.
Unloaded
TNT/Ti wire
DOX loaded
TNT/Ti wire
Multidirectional
DOX(red)
infiltration into
the tissues
(A) Cell death
near DOX
loaded TNT/Ti
(B) Unloaded
TNT/Ti : No
cell death
(C) Live Cells
adhering to
TNT/Ti wire
(A) (B) (C)
DOX Loaded = 33 µg
Burst Release = 13 µg
100% Release = 7 Days
Total release
Burst
Release