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Materials Chemistry
Cite this: J. Mater. Chem., 2011, 21, 12145
www.rsc.org/materials PAPER
Electrochemically assisted deposition of biodegradable polymer nanoparticles/
sol–gel thin films
Efrat Gdor and Daniel Mandler*
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Received 24th March 2011, Accepted 3rd June 2011

DOI: 10.1039/c1jm11262g
Published on 13 July 2011 on http://pubs.rsc.org | doi:10.1039/C1JM11262G

Biodegradable nanoparticles represent a promising platform for controlled release and other
applications in medicine. To alter the interface of the medical device with the living tissue successfully,
a thin coating needs to be applied onto the surface. The traits and functionality of the coating depends
on its components, which in the presented work are sol–gel and biodegradable nanoparticles (NPs)
deposited onto the substrate using the electrochemical sol–gel method. Aspects affecting the deposition
process were investigated such as the applied potential and its duration. The properties of the deposits
with emphasis on the biodegradable NPs within the deposited films were characterized and studied.
Another element examined was the loading ability of the NPs. A fluorescent organic molecule was
incorporated in the biodegradable NPs as a drug model, to demonstrate loading capability.

Introduction results in inhomogeneous layers. Nevertheless, the latter is the

most applied approach for coating medical implants.10,13,14
One of the more significant and therefore researched aspects in Electrochemistry, on the other hand, offers a relatively simple
medicine is the interface between the living tissue and the medical approach to coat complex geometries with thin homogeneous
device, which is mostly altered by a coating layer. The device can films. Organic polymers as well as inorganic materials, e.g.,
be coated with various materials, spanning from polymers1–4 to oxides have been electrodeposited to obtain protective thin films
drugs,5,6 and the coating procedure can be carried out in on medical devices.15 More recently, we have reported on the
a number of methods, such as dip-, spin- and spray-coating,7–10 formation of organic–inorganic polymers based on the sol–gel
depending on the nature of the substrate. technology by electrochemical means.16 Specifically, the appli-
Biocompatible and biodegradable materials have become an cation of either negative or positive potentials in protic media
increasingly important component in medical devices. Biode- alters the pH on the electrode surface, which catalyzes the
gradable polymers are materials that are eroded by natural condensation of the sol–gel precursors. The electrochemical
processes such as hydrolysis.11 When considering medical deposition of sol–gel is a selective process17 (driven on the con-
applications, these polymers must meet certain needs. The ducting parts of the substrate) which can be manipulated and
possible applications range from sutures through temporary tailored according to necessity. One of the advantages intro-
organ replacements to permanent implants. Currently, the duced by this method is the incorporation of elements within the
general desire is to reduce surgical intervention to the minimum sol–gel matrix via the selective deposition.18–21 It is this specific
and minimize exposure to infection and other risks. As a result, advantage we exploit in this research.
there is high motivation to tailor the interfacial properties of Although electrodeposition of sol–gel was first reported over
medical devices. An appealing approach for achieving this goal is a decade ago,22 the electrochemical codeposition of organic
to apply biodegradable polymers as the coating matrix. The most nanoparticles (NPs) within the sol–gel matrix has not been
common biodegradable polymers are poly(lactic acid) (PLA), reported. Electrochemical codeposition of different substances,
poly(glycolic acid) (PGA) and their copolymer, poly(lactic-co- such as metal ions,23 metallic NPs,24 dye molecules25 and corro-
glycolic acid) (PLGA).12 sion inhibition agents,26 have been reported. This work is the
The current procedures for coating medical devices and in first, to the best of our knowledge, to report the electrodeposition
particularly medical implants meet the requirement for of sol–gel and biodegradable NPs.
simplicity, but lack in other aspects. Using dip- and spin-coating In medicine, biodegradable NPs have become increasingly
is mostly restricted to flat surfaces whereas spray-coating often common, especially in drug delivery.27–29 Remarkable results
have been obtained in the area of controlled release via intrave-
nous and oral administration.30 On the other hand, there are only
a few cases where biodegradable NPs have been utilized as
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem,
91904, Israel. E-mail: [email protected]; Fax: +972-2-6585319; coatings.31–34 For example, Joo et al. showed the controlled
Tel: +972-2-6585831 release profile of Paclitaxel from PLGA NP coatings on coronary

This journal is ª The Royal Society of Chemistry 2011 J. Mater. Chem., 2011, 21, 12145–12150 | 12145
 View Online

stents.33 The depositions were carried out by injecting a colloidal BX6000 microscope (Tokyo, Japan) at l ¼ 365 nm (ENF-
suspension between the stent and a ring exploiting capillary 260CIF, Spectroline, New York, USA).
forces.32 Nam et al. used electrophoretic deposition to coat stents
with curcumin-loaded PLGA NPs, using high potentials (up to
13 V) for long durations (up to 1 h).31 Banai et al. reported Methods
inhibition of in-stent stenosis using substance eluting PLGA NP
Nanoparticles preparation. NPs were prepared using the
coatings on stents.34 A work performed by Dawes et al. suggested
emulsion–diffusion–evaporation technique. This synthesis was
the attachment of drug loaded PLGA microspheres to artificial
carried out according to Kumar et al.36 with modifications.
joints to refrain from recurring joint surgery.35
Briefly, 200 mg of PLA was dissolved in 10 mL ethyl acetate at
Here we present a novel method to electrochemically codeposit
room temperature followed by 2 h stirring in ambient conditions.
hybrid films made of sol–gel and biodegradable NPs. The latter
An aqueous stabilizer mixture containing 100 mg of PVA and
were synthesized by the emulsion-diffusion-evaporation tech-
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30 mg of chitosan in 10 mL acetic acid 2% (v/v) was also stirred

nique. Thin films of tetramethoxysilane (TMOS) and the
for 2 h in ambient conditions. Then, the organic phase was added
synthesized NPs were electrochemically codeposited by applying
Published on 13 July 2011 on http://pubs.rsc.org | doi:10.1039/C1JM11262G

to the aqueous phase under stirring. The resulting mixture was

a constant negative potential on ITO substrates. We investigated
stirred for 3 h at room temperature, and then homogenized at
the parameters affecting the deposition, such as the applied
13 500 rpm for 10 min using a homogenizer. The homogenized
potential and its duration. Finally, we synthesized coumarin-1
emulsion was diluted to 50 mL volume with water. The addition
loaded biodegradable NPs and studied the codeposited films by
was carried out under stirring, which was continued to remove
various methods.
the organic solvent.
The resulting dispersion was centrifuged at 7500 rpm for 15
Experimental min, followed by decantation. The decanted liquid was concen-
Materials trated to 10 mL by evaporation under reduced pressure. Fluo-
rescent NPs were prepared simply by adding 5 mg of coumarin-1
Poly-(D,L-lactide) (PLA, Mw ¼ 75 000–100 000 g mol1), chito- to the organic phase in the first step of the synthesis.
san 75–85% acetylated, poly(vinyl alcohol) (PVA, 99%), tetra-
methoxysilane (TMOS, 98%) and coumarin-1 (99%) were Sol–gel preparation. The precursor solution consisted usually
purchased from Sigma-Aldrich. Potassium nitrate ($99.0%), of 0.2 mL TMOS, 11.3 mL water and 1 mL HCl 0.1 M added in
acetonitrile (ACN) and ethanol (99.9%) were acquired from the detailed order; this mixture was hydrolyzed for 1 h, either in
Merck, sodium chloride (99.0%), hydrochloric acid 32% and ambient conditions, or at 40  C with gentle stirring.
acetic acid (99.7%) from J. T. Baker, ethyl acetate (99.5%) and
acetone (AR) from Frutarom (Haifa, Israel). All chemicals were Deposition solution. Electrochemical deposition was conducted
used as purchased. in 12.5 mL of the hydrolyzed sol–gel solution to which 2.5 mL
Deionized water (18.3 MU cm1, EasyPure UV, Barnstead, (unless otherwise specified) of the NPs dispersion and KNO3 to
UK) was used for all the experiments. Indium tin oxide (ITO) a final concentration of 0.1 M were added.
plates 7  50  0.7 mm3, Rs ¼ 15–25 U) were supplied by Delta
technologies Limited (Stillwater, MN, USA). Electrodeposition. A constant negative potential (0.8 to
1.2 V vs. Ag/AgBr) was applied to the ITO electrodes for 1–30
Instrumentation min. The immersed electrodes were then withdrawn from the
deposition solution while still applying the constant potential
The size and charge of the NPs were measured by a Nano ZS
and dried for 24 h in ambient conditions.
zetasizer (Malvern instruments, UK). Electrochemical experi-
ments were conducted using an AutoLab potentiostat (mAutolab
Type II, EcoChemie, Utrecht, The Netherlands). Electro-
Characterization
chemical depositions were carried out using a conventional three-
electrode cell: the working electrode was an ITO plate, the For z potential (ZP) measurements NaCl was added to the NPs
reference electrode was a home-made Ag/AgBr quasi-reversible dispersion to achieve an electrolyte concentration of 20 mM. The
electrode (QRE), and the counter electrode was a Pt wire (99.99% measurements of ZP as a function of pH were carried out by
purity). The working electrodes were withdrawn from the preparing 3.6 mL solutions with calculated pH followed by
deposition solution using a home-made lifter with a velocity of adding a fixed amount of NPs dispersion (400 mL). The pH was
ca. 0.366 mm s1. Step height measurements were performed measured just prior to the ZP measurement.
using a P-15 profilometer (KLA-Tencor Co., San Jose, CA, HR-SEM images were acquired after sputtering the deposits
USA) by creating a notch in the film with a wooden stick after with a thin Pd/Au film to increase the surface conductivity. Cyclic
drying for one day. In the course of preparation of the NPs voltammetry (CV) of the coumarin-1 loaded NPs and TMOS
several appliances were used: Ultra-Turrax T25 homogenizer coated plates were carried out in 20 mM NaCl solution, from 0.0
(Janke and Kunkel GmbH KG, Staufen, Germany) and CN-820 to 1.5 V and a scan rate of 100 mV s1. Degradation of the
centrifuge (MRC, Israel). Images of the coatings were obtained electrochemically codeposited NPs in ACN was carried out by
by high resolution scanning electron microscopy (HR-SEM immersing the coated ITO plates in ACN : water (3 : 1 v/v) for
Sirion, FEI Company, USA). Images of the fluorescent coatings different durations followed by washing with water, after which
were acquired by a fluorescent microscopy using an Olympus the plates were left to dry in air.

12146 | J. Mater. Chem., 2011, 21, 12145–12150 This journal is ª The Royal Society of Chemistry 2011
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Results and discussion

In the last few years, TMOS-based sol–gel films have been used
as biocompatible matrices.37 Biodegradable polymer based NPs
have also been extensively used for medical uses, e.g. drug
delivery.38–41 Our intention was to combine the two in order to
form a framework-like matrix consisting of sol–gel and NPs.
The preparation of the NPs, as depicted in the previous
section, was carried out using the emulsion–diffusion–evapora-
tion technique.36 Post synthesis, the size and z potential of the Fig. 2 Schematics of the experimental system.
NPs were measured to be 97.4  12.4 nm and 46.4  6.3 mV,
respectively. These measurements were performed after centri-
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fugation, which removed the larger particles of micrometre size.

Clearly, the positive potential is attributed to the amino moieties
Published on 13 July 2011 on http://pubs.rsc.org | doi:10.1039/C1JM11262G

of the chitosan polymer. Moreover, the charge of the NPs is pH

dependent, vide infra. The z potential (ZP) mentioned above was
measured by diluting the NPs dispersion in water to give pH 4–5.
Fig. 1 shows the ZP as a function of pH of the NPs dispersion.
Small volumes of the dispersion were added into a buffered
solution (final dilution by a factor of 10), which explains the low
values of the z potential shown in Fig. 1.
Expectedly, as the pH increases the ZP decreases which indi-
Fig. 3 (A) Cyclic voltammetry of an ITO electrode in the deposition
cates a decrease in the stability of the NPs. At pH ca. 7 the z
solution, scan rate equals 100 mV s1. (B) Current–time transient of the
potential is zero, which is in agreement with the pK of chitosan deposition process using an ITO electrode. The potential of deposition
that is ca. 6.8–7.2.42–45 In addition, turbidity was observed in the was 0.9 V.
dispersion sample for this measurement. Evidently, at this pH the
NPs are no longer stable and thus aggregate. In the high pH
region, the ZP is slightly negative, indicating that the NPs are by applying a negative potential to an ITO electrode. Water and
slightly negatively charged which can be attributed to the oxygen reduction leads to hydroxide evolution which catalyzes
adsorption of OH or some deprotonation of PVA. both the condensation of the sol–gel hydrolyzed monomers and
Our goal has been to deposit biodegradable NPs by altering the aggregation of the NPs. This resulted in the formation of thin
the pH electrochemically. In principle, this could have been sol–gel/NPs film on the electrode surface.
achieved by applying a negative potential in a dispersion of these To assess the potential needed for the deposition, we first
NPs. The reduction of oxygen and water should increase the conducted cyclic voltammetry (CV), shown in Fig. 3. The CV is
concentration of hydroxyl ions on the electrode surface and typical for an aqueous solution consisting of sol–gel precursor.
induce the precipitation of the NPs. However, our attempts to That is, a reduction wave that commences at 0.7 V vs. Ag/AgBr
carry out such experiments failed. Inhomogeneous and discon- QRE is seen and attributed to the reduction of water. Based on
tinuous thin films were formed. The introduction of sol–gel, due our experience the current needed for efficient sol–gel electro-
to its biocompatibility, as a means of assisting the electro- deposition is at least 0.25 mA cm2. We applied a potential of at
chemical deposition was a logical next step. Fig. 2 shows sche- least 0.8 V.
matically the essence of our approach. Specifically, codeposition
was carried out in a TMOS solution that was hydrolyzed under
acidic conditions prior to the electrochemical process. After the
hydrolysis, electrolyte and NPs dispersion were added, followed

Fig. 1 z Potential of the biodegradable NPs dispersion in solutions with Fig. 4 HR-SEM image of NPs/TMOS codeposited film on ITO at 1.1
different pH. V for 15 min.

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As seen in Fig. 5A, the thickness of the film increased with the
time that a sufficiently negative potential was applied. As long as
the potential is applied, the reduction of water continues and the
deposit accumulates. A longer deposition than 20 min was not
carried out, however according to the trend as well as our
previous experience in electrochemical sol–gel deposition, the
thickness will reach a plateau. It should be noted that the
deposition solution was continuously stirred. Since the electro-
Fig. 5 The effect of the deposition time (A) and potential (B) on film chemical reaction takes place at the electrode/film interface,
thickness. All other parameters are as in Fig. 4. whereas deposition occurs at the film/electrolyte interface, it is
plausible that the growth of the film will cease as the pH at the
film/electrolyte interface approaches that of the bulk. Thicker
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Fig. 3B shows the chronoamperometry recorded with an ITO

films obtained as a result of longer deposition times were porous
electrode upon applying 0.9 V in an aqueous solution consist-
or discontinuous, which is evident by the penetration of elec-
Published on 13 July 2011 on http://pubs.rsc.org | doi:10.1039/C1JM11262G

ing of the sol–gel precursor (TMOS), NPs and electrolyte. As can

troactive species across the formed layer.
be seen, the current first peaks, then decays to a constant value.
Another studied aspect was the effect of the deposition potential
The peak is a result of the charging current and other effects, and
on the film thickness (Fig. 5B). Chronoamperometry was used,
the decay is due to the faradic processes occurring, i.e. water
whereby a constant potential was applied for a given time. Simi-
reduction. Since deposition was carried out in water, the current
larly to the deposition time effect, the more negative the deposition
decays to a constant value.
potential applied, the thicker the film formed. Yet, there is
A SEM image of a resulting codeposition is shown in Fig. 4.
a threshold potential, ca. 0.8 V, required to electrochemically
The deposit is clearly of a dual nature: spherical shapes, which
codeposit the NPs/sol–gel. The effect of the negative potential on
are connected by patches with no defined shape. The average size
deposition is significant because it affects not only the thickness but
of the spherical shapes as measured in the image is consistent
also the quality of the film. As we apply more negative potential the
with the size measured by dynamic light scattering, i.e. 97.4 
rate of hydroxide evolution increases, which explains the increase
12.4 nm. According to energy dispersive X-ray spectroscopy
of film thickness for a given time. In addition, the higher reduction
(EDS) results, the spherical shapes are the biodegradable NPs,
rate resulted in more aggressive evolution of hydrogen, interfering
and the patches are the sol–gel that acts as the binding matrix.
with film formation. The gas bubbles generated on the electrode
The concentration of NPs in the film is relatively high, which
surface prevented the formation of the layer on the ITO plate.
alludes to the efficient electrochemical codeposition process.
Consequently, in potentials more negative than 1.3 V hardly any
Blank experiments carried out in the absence of TMOS resulted
deposition was observed.
in inhomogeneous and non-continuous patches of polymer,
In order to further investigate the films, we synthesized NPs
without noticeable NPs.
that were loaded with coumarin-1, a fluorescent compound that
To improve and optimize the deposition process we examined
was incorporated in the NPs in the course of the synthesis. The
a number of parameters, which we suspected to control it. The
NPs were thereafter used to produce thin films on ITO using the
applied potential and its duration were first studied. Fig. 5A
same electrochemical method for the codeposition with TMOS.
shows the film thickness dependency on the deposition time. The
Since coumarin-1 is fluorescent, we were able to obtain a fluo-
potential applied was 1.1 V.
rescent image of the codesposit, as seen in Fig. 6. The micrograph
was taken under illumination at 365 nm. Clear fluorescent
microparticles can be seen that represent mostly aggregates of
NPs. At the same time, bright areas in which individual aggre-
gates cannot be detected are also observable. Due to the fact that
coumarin-1 has relatively low solubility in water, it is conceivable

Fig. 6 Fluorescence micrograph of an electrochemically deposited film

of TMOS and NPs loaded with coumarin-1. The film was deposited by Fig. 7 The first and fifth CV cycles of coumarin-1-loaded NPs/TMOS
applying 1.1 V for 15 min. In the micrograph the film is illuminated in coated ITO electrode in 20 mM KNO3, scan rate 100 mV s1. The
365 nm UV light. codeposition was carried out at 1.1 V for 15 min.

12148 | J. Mater. Chem., 2011, 21, 12145–12150 This journal is ª The Royal Society of Chemistry 2011
 View Online

Assuming a one electron transfer,46 we deduced the number of

molecules per area. The amount, ca. 4.7  108 mol cm2, is well
above a monolayer, by at least two orders of magnitude. This
indicates that the oxidized coumarin-1 is indeed from the NPs.
These findings are in agreement with those from the fluorescent
micrograph. Hence, we conclude that the amount of accessible
coumarin-1 is very large.
Recalling that the NPs are biodegradable, we examined their
degradation as a result of exposing the films to a mixture of
acetonitrile and water (Fig. 8). Such mixture has been reported as
a hydrolysis promoter of polyesters.47 Therefore, the coated
plates were immersed in this mixture of ACN and water for
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different durations.
As can be seen from Fig. 8, 5 minutes of immersion in the
Published on 13 July 2011 on http://pubs.rsc.org | doi:10.1039/C1JM11262G

ACN : water mixture was sufficient to induce almost complete

degradation of the NPs on the surface. The size of the remaining
holes in the sol–gel matrix was consistent with the measured size
of the NPs. The rapid degradation might have been assisted by
the dissolving qualities of the ACN, although the degradation is
self-catalyzed, as suggested by previous works.47 The holes form
a pattern in the surface which supports our hypothesis that the
particles are embedded in the sol–gel matrix and are not cova-
lently bound to it, in which the interaction is stronger.

Fig. 8 HR-SEM images of electrocodeposited biodegradable NPs/

Conclusions
TMOS thin films on ITO after (A) 5 min, (B) 1 h in a 3 : 1 mixture of
ACN : water. Electrochemical codeposition of thin biodegradable NPs/TMOS
films on ITO plates was demonstrated, as well as the different
parameters controlling the deposition. The process utilizes
that it is accommodated within the NPs or at least on their a negative potential to generate a change in the pH in the vicinity
surface. This means that the solution itself does not contribute to of the electrode to induce precipitation of both the sol–gel olig-
the observed fluorescence. Furthermore, since the darker parts of omers and the nanoparticles. This approach is not limited to
the micrograph are not entirely black, we suggest that NPs are ITO, but is applicable to other conducting surfaces. In addition,
located within the entire film, and not only on the surface. It is the electrochemistry allows coating of complex geometries as
likely that a significant fraction of the fluorescence originating well. Given that the film thickness is in microns, this approach
from the NPs within the film is absorbed by the sol–gel matrix. fits well with different applications such as coating of stents and
Most of the foreseen medical applications using NPs require other medical devices, to alter the interface. In this work we
accessibility and controlled release of the substance loaded in the demonstrated the possibility of incorporating a substance within
particles. Electrochemistry can provide a simple and quantitative the NPs and their degradation, which suggests the prospect of
tool for estimating the accessibility of incorporated electroactive incorporating drugs for controlled release. This, of course,
species. CV revealed that coumarin-1 (as well as other coumarin requires further research.
derivatives)46 is electroactive and undergoes irreversible oxida-
tion. This enabled us to determine the amount of accessible
coumarin-1.
Notes and references
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