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Electrochimica Acta 56 (2011) 9887– 9892

Contents lists available at SciVerse ScienceDirect

Electrochimica Acta

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ynthesis of polypyrrole nanowire network with high adenosine triphosphateelease efficiency

iaoning Rua,b, Wei Shia, Xiang Huanga, Xin Cuia, Bin Renb, Dongtao Gea,∗

Biomedical Engineering Research Center, Department of Biomaterials, College of materials, Xiamen University, Xiamen 361005, ChinaState Key Laboratory for Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China

r t i c l e i n f o

rticle history:eceived 13 June 2011eceived in revised form 13 August 2011ccepted 18 August 2011vailable online 26 August 2011

a b s t r a c t

A novel drug release system based on polypyrrole (PPy) nanowire network is developed for controlledadenosine triphosphate (ATP) release. Interestingly, the formation of the PPy nanowire networks isinduced by ATP itself, i.e. ATP serves as both the morphology-directing agent and the model drug. Moreimportantly, it should be pointed out that using ATP as morphology-directing agent for the formation ofthe PPy nanowire network can significantly increase the ATP release efficiency due to the high surface

eywords:olypyrrolesrug delivery systemsonducting polymersdenosine triphosphate

area of the resulting nanowire network. The experiment results show that ATP release efficiency increasesfrom 53% (for conventional cauliflower-like PPy) to 90% (for PPy nanowire network) within 45 h uponelectrical stimulation.

© 2011 Elsevier Ltd. All rights reserved.

anowire network

. Introduction

During the past decades, conducting polymer (CP) nanostruc-ures have become a rapidly growing field of research because theysually exhibit novel properties based on their nanoscale size. PPyanowire network is one of the most common nanostructures ofPs and has been synthesized by many research groups using vari-us methods, such as functional molecule-induced synthesis [1–6],eeded growth [7], and interfacial polymerization [8]. The appli-ations of the PPy nanowire network in the fields of biosensors,nergy source, and electronics have also been extensively explored9]. However, to the best of our knowledge, there is no report on these of PPy nanowire network for controlled drug release. Consid-ring the widespread application of conventional PPy in this field10], it is necessary and important to investigate the drug releaseunction of the PPy nanowire network.

In the present work, a drug release system based on PPyanowire network is developed for controlled adenosine triphos-hate (ATP) release. Interestingly, the formation of the PPyanowire network is induced by ATP itself, i.e. ATP serves as bothhe morphology-directing agent and the model drug. ATP is recog-

ized as an important neurotransmitter or co-transmitter in bothhe central and peripheral nervous system, and thus its incorpo-ation into a CP matrix could be of great interest in the study

∗ Corresponding author. Tel.: +86 592 2188502; fax: +86 592 2188502.E-mail address: gedt@xmu.edu.cn (D. Ge).

013-4686/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.oi:10.1016/j.electacta.2011.08.063

of cell metabolism, neuron science, and drug delivery [11]. As aresult, ATP has become one of the most frequently reported modeldrugs related to CP-based drug delivery systems [12–18]. How-ever, so far it has not found application as morphology-directingagent in the synthesis of CP nanostructures. It should be notedthat using ATP to guide the growth of the PPy nanowire net-work for controlled ATP release could significantly increase theATP release efficiency due to the high specific area of the nanowirenetwork. Our experiment results show that ATP release efficiencyincreases from 53% (for conventional cauliflower-like PPy) to 90%(for PPy nanowire network) within 45 h upon electrical stimulation.Furthermore, self-powered ATP release from the PPy nanowire net-work is achieved by coating a thin magnesium layer on the surfaceof the nanowire network. It is found that ATP release efficiency ofthe self-powered system is also much higher than that of the non-nanostructured PPy (coated by magnesium layer as well) and theATP release rate can be tuned by forming a patterned magnesiumlayer.

2. Experimental

2.1. Chemicals

Pyrrole was purchased from Sinopharm Chemical Reagent Co.,Ltd. (China), distilled under the protection of nitrogen gas andstored frozen. ATP was purchased from Sigma. All other chemicalswere of analytical grade and were used as received.

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mechanism is not clear, the presence of the pre-layer may improvethe polymer growth by providing a more rough surface and thushigher surface area of the electrode.

888 X. Ru et al. / Electrochim

.2. Synthesis of PPy nanowire network

The PPy nanowire network was synthesized electrochemicallyt room temperature in a one-compartment cell by the use ofK2005A Electrochemical Workstation (Lanlike Chemistry & Elec-ron High Technology Co., Ltd., China). A titanium layer of 500 nmas magnetron sputtered onto a 4 in. Si wafer. A working electrodeith an active area of 8 mm × 16 mm was cut from this piece. The

i layer was treated before use by the method described in Ref. [19]o enhance the adhesion between Ti and PPy film. A platinum wireas applied as a counter electrode. All potentials were referred to

s saturated calomel electrode (SCE). To ensure the whole surfacef the electrode covered by PPy nanowire network, a thin layer ofPy about 1 �m with conventional morphology was synthesizedrstly on the Ti electrode in an electrolyte containing 0.14 M pyr-ole and 0.07 M lithium perchlorate at 1.0 V for 150 s. Then PPyanowire networks were grown for 600 s from 0.07 M lithium per-hlorate, 0.20 M ATP and 0.15 M pyrrole on the surface of the firstPy layer at 1.0 mA cm−2. Prior to the electropolymerization, thelectrolyte solution was degassed with a nitrogen flow for 15 min.fter polymerization, the working electrode was removed from thelectrolyte and rinsed thoroughly with de-ionized water, and thenried in air at room temperature. For comparison, two kinds ofauliflower-like PPy were synthesized. The first kind of cauliflower-ike PPy was prepared by galvanostatic method under the sameonditions as above except for the absence of ATP. The second kindf cauliflower-like PPy was synthesized from 0.07 M lithium per-hlorate, 0.20 M ATP and 0.15 M pyrrole at the current density of.6 mA cm−2 for 375 s.

.3. Characterization and measurement

The surface morphologies of the prepared PPy were examinedy a scanning electron microscope (SEM, LEO1530, Germany) oper-ted at 20 kV. Cyclic voltammetric (CV) measurements were maden 0.1 M NaCl solution between potentials of −0.6 V and 0.8 V (scanate: 20 mV/s), with a LK2005A Electrochemical Workstation at5 ◦C. The electrochemical impedance spectrum (EIS) of the PPyroducts was measured in 0.1 M NaCl solution at 25 ◦C with aG&G263A potentiostat/galvanostat (Princeton Applied Research,SA) and a Model 5210 Lock-in Amplifier (Princeton Appliedesearch, USA) using 10 mV (rms) AC sinusoid signal at a frequencyange from 100 kHz to 1 Hz. All the data reported are the averagealues of at least 3 samples from each experimental condition.

.4. ATP release

.4.1. External powered ATP releaseThe external powered ATP release from the PPy nanowire net-

ork was carried out in 5 mL NaCl solution (0.9%) stirred with aagnetic stirring bar at room temperature. A negative potential of0.80 V was applied. Samples (2.5 mL) were taken at specific times

rom the release medium, analyzed for ATP content by UV/vis spec-rophotometer (UV-2000, Unico (Shanghai) Instrument Co., Ltd.)t 257 nm, and replaced with an equal volume of fresh 0.9% NaClolution.

.4.2. Self-powered ATP releaseFor self-powered release, a thin layer of magnesium with

hickness of 500 nm was magnetron sputtered with or without aask on the surface of the nanowire network using the JS-3X-

00B magnetron sputtering machine (Chuangweina Technology

o., Ltd., China). In order to obtain a patterned surface, the surfacef the nanowire network was selectively exposed to magnetronputtering atmosphere by using a mask containing square holesf 2.5 mm × 2.5 mm. Only the exposed regions were covered by

ta 56 (2011) 9887– 9892

magnesium layer. As a result, PPy nanowire network with pat-terned magnesium layers on their surface was obtained afterremoval of the mask. Then the ATP release was conducted byimmersing the magnesium-coated PPy nanowire network (pat-terned or non-patterned) vertically in the same release mediumas above except that the external electrical stimulation was notapplied.

3. Results and discussion

3.1. Synthesis of the PPy nanowire network

In our experiment, if PPy nanowire network was depositeddirectly on the Ti electrode, it could not form a continuous film.To circumvent this problem, a non-nanostructured thin PPy layerwas synthesized first on the Ti electrode and it was found that thispre-layer significantly improves the formation of the continuousnanostructured film and the whole electrode surface was coveredcompletely by the PPy nanowire networks. Although the exact

Fig. 1. SEM images of: (A) PPy nanowire networks (inset: high magnification image);(B) cauliflower-like PPy synthesized in the absence of ATP.

X. Ru et al. / Electrochimica Acta 56 (2011) 9887– 9892 9889

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Fig. 2. SEM images of PPy products synthesized at different concentratio

A representative scanning electron micrograph (SEM) of PPyanowire network is presented in Fig. 1A. It can be seen clearlyhat nanowire network with numerous interconnected micro- orano-pores was obtained in the presence of ATP. However, onlyauliflower-like product was formed when the synthesis of PPyas conducted in the absence of ATP (Fig. 1B), which means thatTP plays an important role in the formation of the PPy nanowireetwork.

Structurally, ATP consists of the adenine nucleotide (riboseugar, adenine base, and phosphate group, PO4

2−) plus two otherhosphate groups. The oxygen atoms of the phosphate anion can

orm hydrogen bond with the N–H group of the pyrrole molecule,hich favors the self-alignment of the pyrrole oligomers andnally results in the formation of the nanowire network. How-ver, electrostatic interactions occurred between the positively

TP. (A) 0.02 M, (B) 0.05 M, (C) 0.1 M, (D) 0.15 M, (E) 0.2 M, and (F) 0.25 M.

charged pyrrole/oligomers and anions enhance the random aggre-gation of the pyrrole oligomers. If the electrostatic reaction is muchstronger than the hydrogen bond, the self-alignment of the pyrroleoligomers would be broken. As a result, the random aggregation ofthe pyrrole oligomers leads to the irregular shapes. Therefore, lowATP concentration does not favor the nanowire network formation(Fig. 2A–C). However, with the increase of the ATP concentration,the nanowire network was formed gradually. As shown in Fig. 2D,the PPy nanowire network coexisted with the cauliflower-likePPy at the ATP concentration of 0.15 M. As the ATP concentrationincreased to 0.2 M, only uniform nanowire network was obtained

(Fig. 2E). Further increase of the ATP concentration does not showobvious effect on the morphology of the PPy nanowire network(Fig. 2F). As discussed above, high ATP concentration benefits theformation of the hydrogen bond. Therefore, ordered growth of the

9890 X. Ru et al. / Electrochimica Acta 56 (2011) 9887– 9892

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ig. 3. Percent release of ATP from PPy nanowire networks (�) and cauliflower-likePy (�) upon electrical stimulation of −0.8 V, and from PPy nanowire works (�) andauliflower-like PPy (�) without electrical stimulation.

yrrole oligomers was achieved and the nanowire network wasbtained.

.2. External power controlled ATP release

A negative potential of −0.80 V was applied to the prepared PPyanowire network to stimulate the release of ATP into the solu-ion. For comparison, an ATP doped PPy film with cauliflower-like

orphology was also synthesized from 0.07 M lithium perchlo-ate, 0.20 M ATP and 0.15 M pyrrole at the current density of.6 mA cm−2 for 375 s. The polymerization charge for the forma-ion of the cauliflower-like PPy was equal to that of the synthesis ofhe PPy nanowire network to ensure the amounts of the doped ATPn the two products were the same. The results of ATP release fromoth the nanostructured and cauliflower-like PPy with and with-ut electrical stimulation were shown in Fig. 3. The percentage ofeleased ATP was plotted versus time. As can be seen, the spon-aneous release (without electrical stimulation) of ATP from bothhe PPy products was very slow and there is only a slight differenceetween them. However, ATP release efficiency of the PPy nanowireetwork upon electrical stimulation was apparently higher thanhat of the cauliflower-like PPy. Nearly 90% ATP was released fromPy nanowire network within 45 h, whereas only about 53% ATPas released from cauliflower-like PPy during the same period of

ime.It is reported [20] that CPs release drug most efficiently from

heir surface, as opposed to form within the polymer bulk. Theigger the surface area, the higher the drug release efficiency.herefore, it is reasonably to deduce that the increase of the releasefficiency of nanowire network was due to their high surface areahat derived from their unique network nanostructures.

To further understand the reason for the difference in theTP release efficiency between the PPy nanowire network and

he cauliflower-like PPy, the electrochemical properties of thePy nanowire network were studied by cyclic voltammetry (CV),long with the cauliflower-like PPy for comparison. The cyclicoltammogramm (Fig. 4) shows that both PPy products exhibitlectrochemical activity. The corresponding cathodic and anodic

eaks of the PPy nanowire network are relatively stronger than thatf the cauliflower-like PPy, indicating that PPy nanowire networkas higher electrochemical activity. The charge-transfer capac-

ty of both PPy products was also calculated from the integrated

Fig. 4. Cyclic voltammogramms of bare Ti, cauliflower-like PPy, and PPy nanowirenetwork at a scanning rate of 20 mV/s in 0.1 M NaCl.

area of the cyclic voltammogramm. After electropolymerization,the charge-transfer capacity of the PPy nanowire network is42.5 mC, which is much higher than that of the cauliflower-like PPy(29.8 mC). Considering the distinct morphology difference betweenthe two PPy samples, the increase of the electrochemical activityand the charge-transfer capacity of the nanowire network shouldreasonably be ascribed to its high specific surface area.

Furthermore, the interface properties of the bare Ti, cauliflower-like PPy, and PPy nanowire network were characterized byelectrochemical impedance spectroscopy (EIS). Fig. 5 shows thetypical results of AC impedance spectra. The electron transfer resis-tance (Ret) of the bare Ti was estimated to be 3.19 k�. After coatingby cauliflower-like PPy, the Ret dramatically decreased to 0.51 k�.If the bare Ti was covered by PPy nanowire network, the value fur-ther decreased to 0.08 k�. These results suggest that the formationof PPy, especially PPy nanowire network, can effectively improvethe electron transfer between the solution and electrode.

From the above CV and EIS results, it is clear that the elec-trochemical activity and the charge-transfer capacity of the PPynanowire network are all higher than those of the cauliflower-likePPy, which should also contribute to the high ATP release efficiencyof the nanowire network.

3.3. Self-power controlled ATP release

In our previous works [17,18], we showed that based on thegalvanic cell mechanism, the drugs contained in the CPs could bereleased autonomously without the need of any external powersource by coating a thin layer of active metals such as magne-sium on the surface of the polymers. In the present work, a similarself-powered drug delivery system was constructed by coating athin magnesium layer on the surface of the PPy nanowire networkthrough magnetron sputtering to construct a self-powered systemand then ATP release from this system was investigated. The PPyfilm with cauliflower-like morphology was also coated with thesame thickness of magnesium layer and used as the control. Asshown in Fig. 6, about 22% ATP was released from the magnesium-coated nanowire network after 45 h, which is much higher thanthat of the spontaneous release without the magnesium coating,

confirming the formation of the galvanic cell. The release efficiencyof the magnesium-coated nanowire network was still higher thanthat of the magnesium-coated cauliflower-like PPy. However, whencompared with the result of external electrical stimulation, the

X. Ru et al. / Electrochimica Acta 56 (2011) 9887– 9892 9891

Fig. 5. Electrochemical impedance spectroscopy: Bode plot (A) and Nyquist plot(B) of bare Ti (�), cauliflower-like PPy (©), and PPy nanowire network (�) over afrequency range of 1 Hz–100 KHz in 0.1 M NaCl.

Fig. 6. Self-power controlled ATP release from PPy nanowire networks (�) andcauliflower-like PPy (�).

Fig. 7. (A) The schematic representation of the formation of the self-powered PPynanowire networks. (a) Deposition of nanowire networks on the electrode; (b) coat-ing magnesium layer on the whole surface of the nanowire networks; and (c) coating

patterned magnesium layers on the surface of the nanowire networks. (B) Percentrelease of ATP from the PPy nanowire networks with patterned (�) or non-patterned(�) magnesium layers.

time required for the release of 22% ATP from magnesium-coatednanowire network was significantly longer. This is because thewhole surface of the nanowire networks was covered completelyby the magnesium layer and it is obviously that the magnesiumlayer hampers the ATP release and slows down the ATP releaserate (Fig. 7A).

In order to shorten the time required for ATP release fromthe self-powered network system, a mask was applied before themagnetron sputtering of magnesium. As a result, a patterned mag-nesium layer was obtained on the PPy nanowire network (Fig. 7A).After immersing in the solution, the exposed PPy can directly con-tact with the electrolyte and thus facilitate the ATP release. Asexpected, the time required for release 22% ATP reduced to lessthan 8 h (Fig. 7B). This result indicates that the release rate can betuned by using appropriate mask. It should also be pointed out thatthe release rate could be further changed by altering the size of theexposed area of the mask.

4. Conclusion

In summary, a PPy nanowire network-based drug delivery sys-tem was developed by a facile electrochemical method, in whichATP serves both as morphology-directing agent and model drug.The subsequent release experiments indicated that the release

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fficiency of the system was much higher than that of conven-ional cauliflower-like PPy. Due to the simple synthetic process,igh drug release efficiency, and diverse release modes (eitherxternal power or self-power controlled release), the present sys-em has great potential for application in the field of ATP-relatedrug delivery. Furthermore, the strategy used here, i.e., using drug

tself as morphology-directing agent to prepare drug release sys-em with high surface area and thus high drug release efficiency,

ay be extended to construct other CP-based drug release systems.

cknowledgment

This work was funded by the National Nature Science Founda-ion of China (nos. 31070845, 30870617, 30870648 and 30500127).

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