Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating

doi:10.4236/jbnb.2011.225058

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Journal of Biomaterials and Nanobiotechnology, 2011, 2, 477-484

doi:10.4236/jbnb.2011.225058 Published Online December 2011 (http://www.scirp.org/journal/jbnb)

477

Controlling Drug Release from Titania Nanotube

Arrays Using Polymer Nanocarriers and

Biopolymer Coating

Moom Sinn Aw, Karan Gulati, Dusan Losic*

Ian Wark Research Institute, The University of South Australia, Adelaide, Australia.

E-mail: *[email protected]

Received September 9th, 2011; revised October 14th, 2011; accepted November 10th, 2011.

ABSTRACT

Titania nanotube arrays (TNT) prepared by self-ordering electrochemical anodization have attracted considerable at-

tention for the development of new devices for local drug delivery applications. Two approaches to extend drug re-

lease of water insoluble drugs by integrating TNTs with polymeric micelles and biopolymer coatings are presented in

this work. The proposed strategies emphasized on remarkable properties of these materials and their unique combina-

tion to design local drug delivery system with advanced performance. The first concept integrates TNTs with drug

loaded polymeric micelles (Pluronic F127) as drug nanocarrier, until the second concept includes polymer coating of

drug loaded TNT with biodegradable polymer (chitosan). The water insoluble, anti-inflammatory drug, indomethacin

was used as a model drug. Both approaches showed a significant improvement of the drug release cha racteristics, with

reduced burst release (from 77% to 39%) and extended overall release from 9 days to more than 28 days. These results

suggest the capability o f TNT based systems to be applied for local drug delivery d eliver over an extended period with

predictable kinetics that is particularly important for bone implant therapies.

Keywords: Drug Delivery, Titania Nanotubes, Polymeric Micelles, Pluronic F127, Chitosan, Indomethacin

1. Introduction

To overcome limitations of the systemic therapy and

conventional drug delivery systems such as limited drug

solubility which leads to poor biodistribution, poor

targeting and efficacy, uncontrolled pharmacokinetics,

and serious side effects in non-target tissues, local drug

delivery using implantable systems has become accept-

able as an attractive solution to address these challenges

[1,2]. The majority of drugs like antibiotics, anti-cancer

and anti-inflammatory drugs are insoluble in water or be-

come unstable during their transport to the targeted sites,

hence they require special delivery systems [3,4]. Porous

materials have been demonstrated as excellent candidates

for the design of therapeutic implants, not only because

porous structures support tissue integration, but also be-

cause pores act as remarkable reservoirs for slow drug

elution over extended time periods [5]. Advances in

nanoscience and nanotechnology have led to the devel-

opment of several new nanoporous materials for local

drug delivery administrations. Among them, vertically

aligned titania nanotube (TNT) arrays on Ti surfaces

prepared by self-ordering electrochemical anodization

has been recognized as one of the most promising solu-

tions for the development of advanced implantable and

local drug delivery systems [6,7].

TNTs have excellent biocompatibility, thermal and

chemical stability, controllable dimensions, tunable sur-

face chemistry and high surface-to-volume ratio due to

their long and well aligned hollow nanotube structures.

These advantages render favourable for bone cell growth,

cell differentiation, and apatite-forming abilities, which

make TNTs ideal platforms for bone drug delivery ap-

plications [8-10]. The application of TNT films for im-

plantable medical devices such as orthopaedic implants,

vascular stents, immunoisolation capsules, dental im-

plants, for the prevention of bacterial adhesion, and

growth support for bone and stem cells has been recently

reported [11-15]. For drug delivery applications of TNTs,

it is important to achieve controlled and sustained release

pattern with uniform drug elution over time. Controlling

the pore diameters and lengths of TNTs by anodization

process is used as a simple method to control drug re-

Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating

478

lease characteristics, but this method has considerable

limitation for applications where sustained drug release is

required [16]. In our previous studies, we showed that the

surface modification of pore structures via plasma poly-

merisation that allows control over pore diameter, has the

potential to significantly improve drug delivery perfor-

mance of porous and nanotubular materials [17-20].

Even, progress is encouraging; the development of new

strategies able to provide sustained and controllable drug

release is still required. The integration of TNTs with

nanocarriers and biodegradable polymers currently used

for designing of nanoparticle drug delivery systems,

seems to be a promising approach to advance delivery

and biocompatibility properties of this material.

Strategies to protect sensitive drug molecules in bio-

logical environment and to prevent their precipitation, i.e.

keeping drug molecules solubilised at implant sites

would be beneficial for local implant therapies and nano-

carriers such as polymeric micelles are excellent candi-

dates for molecular solubilisation of hydrophobic drugs

[21,22]. Due to their specific colloidal structure (size

range of 20 - 100 nm) with a lipophilic cargo space for

drugs segregated from the environment by hydrophilic

corona like polyethylene glycol (PEG), polymer micelles

can shield drugs against degradation and solubilise/

molecularly disperse lipophilic drugs in biological envi-

ronment [22].

In this work, we present two approaches to explore

sustained drug release from TNTs using polymer mi-

celles as drug nanocarriers and coating TNT with bio-

compatible polymers. The schematics are presented in

Figure 1. The first strategy (Figure 1(a)) is to encapsu-

late drugs inside polymeric micelles with the aim to

achieve an extended drug release from TNTs for water

insoluble and sensitive drugs. Pluronic F127, a common

triblock polymer, consisting of a central hydrophobic

block of polypropylene glycol (PPO), connected by two

hydrophilic blocks of polyethylene glycol PEO), was

selected for the preparation of polymeric micelles as

nanocarrier, because it is biodegradable, biocompatible,

water soluble and provides enhanced drug/protein stabil-

ity [23]. The release of micelles from TNTs is based on

diffusion process and due to their size (20 nm) and inter-

action with the nanotubes wall surface; their release is

expected to considerably slower than drug molecules.

The second approach to control release kinetics of drugs

from TNTs is to employ the coating of a thin polymer

layer on the top of drug loaded TNTs (Figure 1(b) ). De-

pending on the film thickness, chemical properties and

degradability of this polymer film, a controllable and sus-

tained drug release is proposed to be achievable. In this

work, chitosan, biocompatible and biodegradable poly-

mer, was selected, as it is recognised as an ideal material

for implantable drug delivery systems because of its

proven antibacterial, and osseointegration properties [24].

Chitosan has structural characteristics similar to glycol-

saminoglycans, especially to hyaluronic acid, which is

abundant in the extracellular matrix, with the ability to

attract proteins, promote cell attachment and enhance

implant integration, providing additional and consider-

able advantage to the implant [24,25]. Indomethacin, a

non-steriodal anti-inflammatory drug, was selected for

Figure 1. Schematic diagrams of two approaches used for extended drug release from titania nanotube (TNT) arrays. (a)

Pluronic F127 polymeric micelle as nanocarrier was used for encapsulating the water insoluble drug (indomethacin) and (b)

chitosan polymer layer coated on the top of TNT was used to co ntrol release of drug from nanotubes. PBS = Phosphate bu ff-

red saline.

Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating479

this study as the model of water insoluble drugs [26]. The

drug release characteristics of these two systems are ex-

plored to demonstrate their potential for the development

of TNTs as drug eluting implants with extended drug

release characteristics.

2. Materials and Methods

2.1. Materials

Titanium foil, Ti (99.9% purity), with a thickness of 0.25

mm, was supplied by Alfa Aesar (USA). Ethylene glycol,

ammonium fluoride, chitosan (low molecular weight,

75% - 85% deacetylation), and indomethacin (>99%

TLC), Pluronic® F127 (Bioreagent, average Mw~12,600)

were obtained from Sigma Aldrich Co. (Australia). Dialy-

sis sacks (avg. flat width of 35 mm) were ordered form

the same company. High purity water, ultra-pure Milli-Q

grade (18.2 M·Ω·cm) with a final filtering step through a

0.22 m filter was used. All chemicals were of analytic

reagent grade and used without further purification.

2.2. The Fabrication of Titania Nanotube (TNT)

Arrays on Ti

To prepare a TNT layer on Ti foil (TNT-Ti), two anodi-

zation steps were performed using a specially designed

electrochemical cell and computer controlled power sup-

ply (Agilent), using previously described procedures [19,

27,28]. A specially designed electrode holder permitted

only a circular area of diameter 1 cm of Ti metal available

for anodization. In the first anodization step, a constant

voltage of 100 V was applied for 2 hours in NH4F/ethy-

leneglycol electrolyte (3% water and 0.3% NH4F) at a

room temperature of 20˚C. The resultant TNT layer was

removed (mechanically followed by sonication), leaving

the nanotextured titanium surface for the second anodi-

zation. The second anodization step was performed using

the same conditions (100 V) as the first anodization, with

an anodization time of 1 hour to make about 50 µm thick

TNTs layer on Ti with perfectly ordered nanotube struc-

tures. The voltage/current, voltage-time, and current-time

signals were adjusted and continuously recorded (Lab-

view, National Instruments) during the anodization proc-

ess to assure the reproducibility of the fabrication process.

2.3. Synthesis of Pluronic Micelles and Drug

Encapsulation

Pluronic F127 micelles was synthesised using the direct

dissolution technique as described previously [29]. 15

mg of micelles were dissolved in 5 ml chloroform and

upon solvent evaporation in a rotary vacuum evaporator;

micelles were dispersed in 20 ml of Milli-Q water.

Samples were then dialysed against Milli-Q water for 2

days to produce the micelle suspensions. The drug (indo-

methacin) was dissolved in chloroform prior to drying

and then added to the micelle solution (10 ml of Milli-Q

water containing 50 mg of micelles) under moderate

magnetic stirring. The remaining chlroform is removed

under reduced pressure via osmosis effect using regene-

rated cellulose membrane (Spectrum Labs, Inc.) of 15

mm flat width with 20 cm long tubing. The size of the

micelles (Pluronic and Pluronic-Ind) before and after

loading were determined by laser light scattering using

Zetasizer Nano (Malvern Instruments) from 5 repeated

measurements.

2.4. Loading of Drug and Drug-Loaded Micelles

into Titania Nanotubes

The prepared TNT-Ti substrates (12 mm ×12 mm) were

loaded with drug and drug-loaded micelles via a simp-

lified lyophilisation method. Micelle dispersion (10 μl)

was pipetted onto the substrate surface and gently spread

to ensure an even coverage. The surfaces were then

allowed to dry under vacuum at room temperature for 2 h.

After drying, the loading step was repeated 20 times until

the appropriate amount of micelles was present in the

nanopore array. The top of the substrates on the end was

carefully cleaned to remove adsorbed micelles from the

surface. A solution of indomethacin (1% w/v) was pre-

pared in ethanol and 10 µl of the drug solution was

loaded into the nanotube surface and allowed to dry in air

for 15 - 20 min. After drying, the TNT surface was wiped

with a soft tissue to remove excess drug from the TNT

surface. The sample was placed in a vacuum dessicator

under vacuum for 1 h to remove the solvent and water.

The cycles of loading, drying and wiping were repeated

25 times to load a sufficient amount of indomethacin

drug into the nanotubes.

2.5. Chitosan Coating of Drug Loaded Titania

Nanotubes

Polymer solutions of chitosan (1% (w/v), chitosan +

0.8% (v/v) acetic acid in deionised water) was prepared.

The dip-coating process was performed by dipping the

TNT-Ti implant into the polymer solution, followed by

drying in an oven at 70˚C for 10 min. The number of

dipping can control the thickness of the deposited

polymer and for this study; we did 5 times of dipping to

make a thicker polymer film. The film thickness of the

chitosan coat of prepared samples (Chit-Ind-TNT-Ti)

was measured using an ellipsometer (Si wafer as control

sample) and cross-sectional SEM imaging.

2.6. Drug and Drug-Micelles Loading and

Release Characterization

To determine the amount of loaded and released drug and

drug-micelles in TNT samples, thermogravimetric ana-

Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating

480

lysis (TGA) was performed (Hi-Res Modulated TGA

2950) after drug and drug-micelles loading, after poly-

mer coating and at the end of the release experiment. In

order to find the correct range of the drug decomposition,

20 - 25 mg drug (indomethacin) was mounted onto the

platinum pan, then heated up to 800˚C at a scanning rate

of 10˚C/min under a nitrogen gas flow of 50 ml/min.

This was performed to obtain its weight loss peak. It was

followed by drug-, (Ind-TNT-Ti) drug-loaded micelle

(Pluronic-Ind-TNT-Ti) and chitosancoated TNTs. The

thermograms were analyzed using TGA data analyzing

software (Universal Analysis, 2000), to calculate the

loading capacity.

In vitro drug release from all prepared TNT samples

(drug and drug-loaded micelles with and without chi-

tosan coating) was investigated by immersing the sam-

ples in 5 ml phosphate buffer (PBS) at pH = 7.4, where

the amount of released drug was measured via UV-Vis

spectroscopy using Varian UV-Vis spectrophotometer.

Measurements were taken at short intervals (every 5 - 15

min) during the first 6 hours to monitor the initial burst

release, followed by testing every 24 h to observe the

delayed release until the total amount of drug was

released into the surrounding PBS. Absorbance was mea-

sured at 320 nm for drug and at 760 nm for drug-loaded

micelles. The corresponding drug concentration was

calculated based on the calibration curve obtained. The

final release profile of each experimental set was ex-

pressed for burst (first 6 hours) and delayed release (7 -

28 days) in a graph with cumulative release (percentage)

vs. time. The release of drug (indomethacin) from TNT

without micelles and chitosan coating is used as the

control for comparing how release can be extended by

these methods.

2.7. Structural Characterization

Structural characterization of the prepared TNT-Ti sub-

strates before and after drug loading and after polymer

coating and drug release were performed using a field

emission scanning electron microscope (SEM) (Philips

XL 30). The samples were cut into small (approximately

10 × 10 mm) pieces, mounted on a holder with double-

sided conductive tape and coated with a layer of platinum

3-5 nm thick. Images with a range of scan sizes at normal

incidence and at a 30 degree angle were acquired from

the top, the bottom surface and cross-sections.

3. Results and Discussion

3.1. Structure and Morphology of Prepared

Titania Nanotube (TNT) Arrays

The structure and morphology of the prepared TNT-Ti

substrates was characterised by SEM and is summarised

in Figure 2. A typical cross-sectional image of free-

standing TNT structures, after removing them from the

Ti substrate (for imaging purposes) is presented in Fig-

ure 2(a). The thickness of the TNT layer was about 50

µm, which was controlled by selecting the appropriate

voltage (100 V) and anodization time (1 hour). A whole

TNT layer with a diameter of 1 cm, formed on a Ti foil

substrate, is shown in Figure 2(a) (inset). SEM images

of the top nanotube surface (Figure 2(b)) show pores

with diameters of 120 ± 20 nm. A high-resolution image

of the cross-sectional SEM image of the TNT layer

shows a vertically aligned and densely packed array of

nanotubes across the entire structure (Figure 2(c)). The

bottom surface of the TNT nanotube layer, after the de-

tachment from the Ti substrate (Figure 2(d)) shows that

the nanotubes were closed with spherical oxide barrier

layer.

For this study, titania nanotubes with pore diameters

~120 nm and a length of 50 µm were prepared, in order

to maximise their drug loading capacity

3.2. Characterisation of Polymeric Micelles

(Pluronic F127) before and after Drug

Encapsulation

The average size of prepared Pluronic F127 micelles was

determined to be 20.0 ± 0.7 nm using dynamic light

scattering measurements (Figure 3). When drug indome-

thacin was encapsulated inside the micelle (hydrophobic

core), the diameter was only slightly increased to 23.0 ±

1.4 nm (Figure 3), showing a minor difference in size

between the drug-loaded and drug-free micelle (~3 - 5

nm). The micelle size was found to be consistent over a

6-month monitoring period, indicating long term stability

Figure 2. SEM image of titania nanotube arrays prepared

on Ti foil by electrochemical anodization showing, (a) side

view (whole structure is shown in inset); (b) the top surface

with open pores; (c) cross-sectional image showing hollow

nanotube structures, and (d) the bottom surface with closed

pores.

Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating481

Figure 3. The size of polymeric micelle (Pluronic F127) be-

fore and after encapsulation of drug (indomethac in).

under a freeze storage condition of 1˚C. As Pluronic

F127 was prepared in dilute solution above its critical

micelle concentration (CMC) and critical micelle tem-

perature (CMT), it is ensured that no gelation occurred

and that it forms self-assembling, non-aggregating mi-

celles in adequate concentration and proper suspension in

PBS [30]. Its hydrophobic PEO blocks associate to form

the core region, whereas the hydrophilic PPO segments

position between the core and the external aqueous me-

dium, serving as an interface between the bulk PBS and

the hydrophobic domain. The amount of Pluronic F127

loaded in TNT nanotubes was 22.6 ± 1.0 wt% as mea-

sured in TGA. The size measurements after release show

no difference confirming the preservation of micelle

structure after its release from TNTs.

3.3. Characterisation of Chitosan Polymer

Coating on Titania Nanotube Arrays

The deposition of chitosan polymers onto drug-loaded

TNT-Ti by the dip-coating process was evaluated by

SEM characterisation. Typical images of a prepared poly-

mer layer showing thick chitosan layer covering the TNT

surface are presented in Figures 4(a)-(b). SEM image

shows a featureless top surface of TNT confirming that

pores were covered by polymer layer. Corresponding

cross-sectional image (Figure 4(b)) confirms the forma-

tion of thick polymer layer. The thickness of this layer

was estimated to be between 2 - 2.5 µm by SEM and

ellipsometry. It was shown, that by controlling the num-

ber of dip-coating it is possible to control the thickness of

the polymer film (data not shown). Thus, the film thick-

ness can be used as controlling parameter to tune drug

release characteristics of TNTs.

3.4. Thermogravimetric Analysis (TGA) of Drug

and Drug Loaded Micelles

Before release studies were performed, TGA measure-

ments were performed to evaluate the loading (wt%) of

drug and drug-loaded micelles into the TNT substrates.

Figure 5 summarises these TGA graphs, showing their

single stepwise decrease of weight loss and loading

characteristics. The temperature change corresponds to

the decomposition temperature for both polymeric micelle

and drug (indomethacin). It was between 200˚C and

375˚C. But, it remains difficult to detect separate micelle

and drug weight loss due to their close temperature range

for vaporisation, Based on the weight loss, the loading

capacity of TNT-Ti substrates for drug or drug-loaded

micelle was determined to be 16.2 to 24.6 wt%, which is

reasonably high. TGA on two control samples including

chitosan-coated and bare (uncoated) titania nanotubes

without drug/micelle loading confirmed that the weight

of both samples remain constant throughout the heating

and that the weight loss of chitosan is negligible, since

Figure 4. SEM images of chitosan coated nanotube titania

arrays with loaded drug showing (a) the top surface and (b)

cross-sectional view.

Figure 5. TGA graphs showing the amount of weight loss

for drug and drug-micelle samples from bare and coated

titania nanotube (TNT) arrays.

Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating

482

lease of drug.

it is an extremely light biopolymer film which comprises

<0.001% of the total sample weight. Results show that cumulative burst release in compa-

rison with the control sample (77%) was significantly

reduced when the drug is loaded in polymeric micelles

(58%) and when drug is loaded in the TNT covered with

chitosan film (39%). Both approaches also showed a

considerably extended overall drug release from 9 days

to 12 and 28 days, confirming their capability to provide

extended release of poorly water soluble drugs. It was

found that a 44.4% improvement (4 days longer) in re-

lease duration was obtained using micelle as the drug

nanocarrier, compared to drug only loaded in titania.

3.5. Controlling Drug Release from TNTs Using

Drug-Loaded Micelle and Polymer Coating

Comparative drug release profiles of drug (indomethacin)

loaded into TNT with and without micelles and with and

without polymer film (chitosan) coatings are presented in

Figure 6. Release characteristics are listed in Table 1, to

shows release efficiency (% drug release) at various time

intervals (1 h, 6 h, 24 h, 7 days, 14 days, 21 days and 28

days). According to Figure 6, all release curves display a

biphasic behaviour (except for the free drug), showing

initial burst release during the first 6 h with 39% to 77%

of release, followed by a gradual, slow release that lasted

from 10 to 28 days. The burst release can be explained

by the high concentration gradient across the pores, with

the large diameter pores (~120 nm) allowing rapid re-

These results suggest that the release behavior of poly-

mer nanocarriers from the nanotube structures is different

from release of small drug molecules. That is expected

because the release kinetics of micelles is based on diffu-

sion process and is influenced by their considerable lar-

ger size (>20 times than drug molecules) showing slower

Figure 6. Comparative drug release graphs of anti-inflammatory drug (indomethacin) from TNTs using polymer micelles as

drug carrier (Pluronic-Ind) and polymer (c hitosan) c oating showing overall and burst dr ug release.

Table 1. Drug release characteristics of drug (indomethacin) and drug loaded micelles (Pluronic-indomethacin) from un-

coated and polymer (chitosan) coated titania nanotubes (TNT). (Mean ± SD, n = 3).

Drug release efficiency (%)

Sample

1 h 6 h 24 h 7 days 14 days 21 days 28 days

Ind (free) 45 ± 1 99 ± 1 100 ± 0 100 ± 0 100 ± 0 100 ± 0 100 ± 0

Ind-TNT 40 ± 1 77 ± 2 88 ± 1 97 ± 2 100 ± 0 100 ± 0 100 ± 0

Pluronic-Ind-TNT 19 ± 2 58 ± 2 68 ± 3 90 ± 3 100 ± 0 100 ± 0 100 ± 0

Chit-Ind-TNT 17 ± 2 39 ± 1 66 ± 2 88 ± 3 90 ± 2 96 ± 3 98 ± 1

Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating483

diffusion from long nanotube structures.

By increasing the size of polymeric micelles, decreas-

ing the diameters of nanotubes or changing the surface

chemistry of TNTs to increase interaction with the mi-

celles it is possible to further extend drug release, show-

ing the flexibility of this approach to control drug deliv-

ery characteristics of TNTs platform.

Figure 6 and Table 1 show that the drug release pro-

files from chitosan coated TNT-Ti have significant changes

with considerably extended drug release (28 days) as a

result of polymer coating. The release kinetics of this sys-

tem is different in comparison with drug loaded micelles

as drug release is mainly controlled by the transport of

drug molecules through the polymer matrix and by the

rate of degradation of the polymer film [31,32]. When

thinner chitosan film was applied (one dip coating) drug

release was significantly reduced to 9 days which con-

firms that the drug release characteristics of polymer

modified TNT-Ti can be tuned by controlling the polymer

film thickness. This is particularly important in the case of

specific applications, to ensure optimal therapeutic dosage

of drug for the required time. Therefore, this approach has

the flexibility to be applied to Ti implants for different

purposes, from short drug release scenarios, for example

to suppress inflammation, moderate term (1 - 2 weeks), to

prevent bacterial infection, or long-term (>30 days) drug

release for other therapies, including improving osseoin-

tegration process, fracture repair or treatment of bone

cancer. Additional advantages of this method are that

chitosan coated TNT-Ti substrates could provide a

greater cell attachment based on positively-charged chi-

tosan chains, with a high density of amino groups which

could attract proteins and promote cell adhesion and pro-

vide superior biocomatability of these structures [33].

4. Conclusions

In summary, we report the preparation of titania nano-

tube (TNT) arrays prepared by self-ordering electro-

chemical anodization, with aim to explore new strategies

to improve their drug release characteristics. Two con-

cepts for controlling and extending drug release of poorly

soluble drugs are demonstrated: the first which integrates

TNTs with drug loaded polymeric micelles as drug na-

nocarrier and the second, which includes the coating of

drug loaded TNTs with biodegradable polymer (chito-

san). The preparation involves simple and inexpensive

processes, including electrochemical generation of TNT

arrays on Ti surface, preparation of polymeric micelles,

drug loading and dip-coating deposition of biodegradable

polymers. Both approaches showed a significant impro-

vement the drug release characteristics of TNTs, with

reduced burst release (from 77% to >39%) and extended

overall release from 7 days to more than 28 days. This

release pattern is especially useful in bone implant thera-

pies that require a large initial dose followed by a pro-

longed maintenance dose over a few weeks. The use of

biodegradable and antibacterial polymer such as chitosan

provides favourable cell adhesion properties and addi-

tional an advantage to enhance integration of implantable

drug delivery device.

5. Acknowledgements

The authors gratefully acknowledge the financial support

and funding from the Australian Research Council

(DP0770930 and LP 0989229) and the University of

South Australia.

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