Microrough Cobalt−Chromium Alloy Surfaces for Paclitaxel Delivery:
Preparation, Characterization, and In Vitro Drug Release Studies
Susan Lancaster, Sandeep Kakade, and Gopinath Mani*
Biomedical Engineering Program, The University of South Dakota, 4800 North Career Avenue, Sioux Falls, South Dakota 57107,
United States
*S Supporting Information
ABSTRACT: Cobalt−chromium (Co−Cr) alloys have extensive biomedical
applications including drug-eluting stents (DES). This study investigates the
use of eight different microrough Co−Cr alloy surfaces for delivering paclitaxel
(PAT) for potential use in DES. The eight different surfaces include four bare
microrough and four self-assembled monolayer (SAM) coated microrough
surfaces. The bare microrough surfaces were prepared by grit blasting Co−Cr
with glass beads (50 and 100 μm in size) and Al
2
O
3
(50 and 110 μm). The
SAM coated surfaces were prepared by depositing a −COOH terminated
phosphonic acid monolayer on the different microrough surfaces. PAT was
then deposited on all the bare and SAM coated microrough surfaces. The
surfaces were characterized using scanning electron microscopy (SEM), 3D
optical profilometry, and Fourier transform infrared spectroscopy (FTIR).
SEM showed the different morphologies of microrough surfaces without and
with PAT coating. An optical profiler showed the 3D topography of the different surfaces and the changes in surface roughness
and surface area after SAM and PAT deposition. FTIR showed ordered SAMs were formed on glass bead grit blasted surfaces,
while the molecules were disordered on Al
2
O
3
grit blasted surfaces. Also, FTIR showed the successful deposition of PAT on
these surfaces. The PAT release was investigated for up to two weeks using high performance liquid chromatography. Al
2
O
3
grit
blasted bare microrough surfaces showed sustained release profiles, while the glass bead grit blasted surfaces showed burst release
profiles. All SAM coated surfaces showed biphasic drug release profiles, which is an initial burst release followed by a slow and
sustained release. SAM coated Al
2
O
3
grit blasted surfaces prolonged the sustained release of PAT in a significant amount during
the second week of drug elution studies, while this behavior was not observed for any other surfaces used in this study. Thus, this
study demonstrates the use of different microrough Co−Cr alloy surfaces for delivering PAT for potential applications in DES
and other medical devices.
1. INTRODUCTION
Cobalt−chromium (Co−Cr) alloys which belong to ASTM
standards F75 (Co-28Cr-6Mo casting alloy), F799 (Co-28Cr-
6Mo thermodynamically processed alloy), F90 (Co-20Cr-25W-
10Ni wrought alloy), and F562 (Co-35Ni-20Cr-10Mo wrought
alloy) have extensive applications in a variety of biomedical
implants and devices including but not limited to cardiovascular
stents, total hip replacements, artificial knee joints, shoulder
and elbow prosthesis, dental restorations, removable partial
dentures, and spinal fixation rods.
1
Co−Cr alloys have either a
smooth or rough surface depending on the intended
application. Microrough Co−Cr alloy surfaces enhance the
osseointegration of orthopedic and dental implants.
2−4
Osseointegration is a process in which the bone grows into
the implant surface without the formation of fibrous tissue at
the interface. Hence, the biomechanical stability of the implants
is greatly improved by the microrough surfaces. Although a
plethora of literature is available on the use of microrough Co−
Cr alloy surfaces for improving the implant-tissue integra-
tion,
2−4
the number of reports available on drug delivery from
these alloy surfaces is rather limited.
Drug delivery from microrough Co−Cr alloy surfaces has
tremendous potential applications in coronary artery stents. A
stent is a small metal mesh tube that is implanted to open a
blocked artery.
5,6
However, the endothelial cell injury caused
during stent implantation leads to a cascade of biological events
resulting in neointimal hyperplasia, which is a pathological
condition in which the smooth muscle cells grow inside the
artery and reocclude it.
7
Drug-eluting stents (DES) which
deliver therapeutic drugs locally to prevent the growth of
smooth muscle cells are currently used in patients.
8,9
However,
there are a few limitations associated with the use of currently
available DES. Polymers are generally used to deliver drugs
from stent surfaces. However, some polymers can cause serious
adverse reactions including late stent thrombosis (LST), which
is a condition in which blood clots occur in the arteries of
patients after months or years of stent implantation.
10−14
The
clinical consequences of LST are catastrophic events including
Received: April 22, 2012
Revised: June 21, 2012
Published: June 22, 2012
Article
pubs.acs.org/Langmuir
© 2012 American Chemical Society 11511 dx.doi.org/10.1021/la301636z | Langmuir 2012, 28, 11511−11526