201 (2007) 6861–6864www.elsevier.com/locate/surfcoat

Surface & Coatings Technology

Radio frequency plasma polymers of n-butyl methacrylate and theircontrolled drug release characteristics

I. Effect of the oxygen gas

Yuan Yuan a, Changsheng Liu a,⁎, Yuan Zhang a, Min Yin a, Chao-ou Shi b

a Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, P.R. Chinab Center of Analysis and Research, East China University of Science and Technology, Shanghai 200237, P.R. China

Available online 24 October 2006

Abstract

The effect of oxygen gas on the chemical structure, surface property and controlled drug release characteristics of radio frequency (RF) plasmapoly-n-butyl methacrylate (PPBMA) thin films was investigated. The ATR–FTIR and XPS spectra of the resultant PPBMA films showedrelatively higher concentration of C–H, C–C and C_C groups, but less intense peaks of C_O and C–O functionalities, which imply that theoxygen gas had no significant influence on the chemical structure of the plasma films. Results of the SEM experiment revealed that a dome-likestructure was observed in the case of deposition without oxygen, but in the case of deposition with oxygen, a smooth and dense surface wasproduced. Moreover, the hydrophilicity of PPBMA obtained from the deposition with oxygen was higher than that without oxygen. Drug releasefrom PPBMA deposition coating without oxygen had biphasic patterns, a fast release followed by a slow release, but the one with oxygenexhibited a slow Higuchi release.© 2006 Elsevier B.V. All rights reserved.

Keywords: Plasma n-butyl methacrylate polymer; Oxygen; Surface property; Controlled drug release characteristics

1. Introduction

Plasma polymerization is a thin film deposition process forthe preparation of polymeric films from a wide variety of sub-strates. Species excited in the plasma can undergo condensationreactions, forming a polymeric material. These reactions canoccur either at the surface of the plasma or in the gas phase. Theproducts can be varied from oily fluids to very hard, dense solids.The characteristics of plasma polymers can be changed byvarying the power, the pressure and flow rate of the monomergas. Carrier gases, such as Ar, O2, or H2, also have an effect onthe properties of some plasma polymers [1–3].

Compared with conventional polymers, plasma polymershave some unique advantages, including ultra-thin film depo-sition, good adhesion, and its stable, durable nature withoutchanging the bulk properties of the substrate. Therefore, plasmadeposition has become an important and unique technique fordeveloping biomaterials with specific surface properties, such as

⁎ Corresponding author. Tel./fax: +86 21 64251358.E-mail address: csliu@sh163.net (C. Liu).

0257-8972/$ - see front matter © 2006 Elsevier B.V. All rights reserved.doi:10.1016/j.surfcoat.2006.09.020

hydrophilicity [4], blood compatibility [5,6] and controlled drugrelease [7,8]. Plasma poly-n-butyl methacrylate (PPBMA)polymer film has been found to be an ideal barrier coating tocontrol drug release [7,8]. However, to the best of our knowl-edge, little work is known so far regarding the effect of carriergas, for example, oxygen, on the physicochemical properties ofPPBMA films and their controlled release characteristics.

This paper describes our early work on the effect of oxygengas on the chemical structure, surface morphology, hydrophi-licity, and drug-controlled release characteristics of RF PPBMAfilms. Drug-eluting system used for the release experiment waspolyethylene vinylacetate (EVA)/paclitaxel matrix on 316Lstainless steel.

2. Experimental methods

The drug-eluting system used for the release experiment wasEVA/paclitaxel matrix on 316L stainless steel. This releasematrix consisted of two layers. The inner layer was EVA poly-mer and 10 wt.% paclitaxel loading, and the outer one was EVApolymer with no paclitaxel.

Table 1Results of deconvolution of the C1s XPS peak—presence of carbon in variouschemical functionalities

Plasmadeposition

Relative fraction, %

284.2 eV(C–H)

285.0 eV(C–C)

285.8 eV(C_C)

286.4 eV(C–OH)

287.1 eV(C–O–C)

287.8 eV(C_O)

Withoutoxygen

29.68 32.66 17.37 8.43 6.68 5.12

Withoxygen

31.85 34.55 13.88 7.58 6.53 5.79

6862 Y. Yuan et al. / Surface & Coatings Technology 201 (2007) 6861–6864

A 316L stainless steel with drug-eluting system was locatedin the center of the RF plasma reaction chamber. The systemwas pumped down to a base pressure of 2.0×10−2 Pa. Prior toBMA deposition, the sample was subjected to a brief treatmentin oxygen plasma (20 Pa, 40W, 20 s) for cleaning. And then, thesystem was evacuated to background pressure again. Pure BMAmonomer or 90 vol.% BMA and 10 vol.% of oxygen mixturewere introduced. The polymerization occurred at 40 W underpressure of 20 Pa for 30 min. The matrices for the release studywere placed in vials containing 4 mL of pure water at 37 °C.Aliquots of the medium were replaced with the same amount offresh water at specific intervals. Paclitaxel concentration wasanalyzed by HPLC. To evaluate the physicochemical propertiesof PPBMA, ATR–FTIR, XPS, SEM and static contact anglemeasurement were applied respectively.

3. Results and discussions

3.1. Chemical structure of the PPBMA coatings

Fig. 1 shows the FTIR spectrum of BMA monomer and theATR–FTIR spectra of the PPBMAs in the case of depositionwithout and with oxygen. It can be seen that there were somedifferences both in terms of intensity and location of absorptionband between BMA monomer and its corresponding plasmapolymers. However, there were little differences in the ab-sorption band between the PPBMA films deposited with andwithout oxygen. Compared with the FTIR spectrum of mono-mer, it was found that, after polymerization, in PPBMA films theC_O stretching band at 1720 cm−1 almost disappeared, and theC–O–C stretching bands at 1295, 1268, and 1168 cm−1

decreased significantly. Besides the C–H stretching bands ofCH3 and CH2 groups at 2963 and 2875 cm−1, the band at1652 cm−1 due to the C_C stretching vibration still existed [9],which suggested a significant unsaturation in the PPBMA films.This is unconventional in PPBMA chemistry. Broad and strongabsorption bands between 3500 and 3100 cm−1 were also ob-served, which may be attributed to the stretching vibrations ofhydrogen-bonded hydroxides [10].

XPS survey scans of the PPBMA coatings deposited withand without oxygen showed the presence of only carbon and

Fig. 1. FT-IR spectra of BMA monomer (a) and ATR–FTIR spectra of PPBMAdeposition (b) without oxygen (c) with oxygen.

oxygen. A narrow scan of the C1s region allowed the detectionof some functional groups created during the plasma treatment.The carbon peaks were fitted according to other reports [10] andthe results are shown in Table 1. The plasma films producedwith and without oxygen all had a higher concentration of C–Hand C–C groups, but less intense peaks of C–O and C_Ofunctionalities. The content of the oxidized carbon was almostnot increased by the addition of oxygen. These results wereconsistent with the FTIR analysis data, further suggesting thatoxygen had little influence on the chemical structure of thePPBMA coatings. This result is somewhat unexpected. Onewould think that the presence of oxygen in the plasma wouldcreate more oxygen-bearing groups, e.g., carboxyl and carbonylfunctionalities. However, the observed result seemed to be incontradiction with that hypothesis, which might be correlatedwith the mechanism of BMA plasma polymerization.

3.2. Morphology of the PPBMA coatings

The surface morphology of the polymer films was stronglyaffected by the oxygen carrier gas. Fig. 2 shows the plane viewSEM images of the deposited PPBMA films. Dome-like struc-ture of nanometer-sized particles was observed in Fig. 2(a) ratherthan in Fig. 2(b). The size of the domes was about 50 nm and thefilm was loose. The film deposited in the presence of oxygen hada uniform, smooth, dense surface.

The change of the roughness of the plasma films could arisefrom several mechanisms. Reaction in the gas phase can lead tothe production of powders; reaction at the surface can result invery flat films [11]. It is believed that oxygen has two basiceffects in the plasma deposition. One is, of course, the dilutioneffect. As the total flow rate was constant, the addition of oxygendiluted the reactive species that formed in the plasma. The otherone, which is more important, is a chemical effect on the com-position of plasma. Oxygen atoms get excited from ground statesto excited states by absorbing energy. This energy of the atomcan dissociate the intermediate molecules via collision. Additionof oxygen to the reaction could reduce the film deposition rate byreducing the number of polymer forming radicals in the gasphase [3]. Consequently, polymerization in the presence ofoxygen occurred mainly on the surface and not in the plasmavolume, resulting in a smooth and dense film. In the absence ofoxygen, the dome-like structure suggested that both particles andintermediates were deposited simultaneously on the substrate,indicating that the condensation reaction of BMA took placeboth in the plasma volume and on the substrate surface.

Fig. 3. Paclitaxel release profiles from control (a), and PPBMA barrier coating inthe case of deposition without oxygen (b) and with oxygen (c).

6863Y. Yuan et al. / Surface & Coatings Technology 201 (2007) 6861–6864

3.3. Hydrophilicity of PPBMA coatings

In order to compare the hydrophilicity of the uncoated andPPBMA-coated films, the water contact angle was measured.The results revealed that a decrease in water contact angle from64.9° for the virgin film to 26° for the PPBMA depositionwithout oxygen and 5.3° for the PPBMA deposition withoxygen, respectively, suggested that after plasma polymeriza-tion, the surface hydrophilicity was significantly improved,especially in the case of deposition with oxygen. These resultsconfirmed again that a brand-new surface, which is completelydifferent from the EVA surface, was produced by the RF-PPtechnique.

3.4. Drug-controlled release characteristics of PPBMA films

Fig. 3 shows the release profiles of paclitaxel from 10%paclitaxel loading EVA matrices on 316L stainless steel beforeand after plasma deposition. Before deposition, paclitaxel wasreleased quickly and the released amount was up to 100% after35 days.

After PPBMA film deposition, drug release rate significantlydecreased. The PPBMA deposition without oxygen showed anirregular release profile as a function of time. The burst release

Fig. 2. SEM. Micrographs of PPBMA coating in case of deposition (a) withoutoxygen (b) with oxygen.

was followed by a slow release. Approximately 55% of pacli-taxel was released in the first 7 days. As the release experimentwas performed continuously, a relatively slow release tookplace, during which about 32% of paclitaxel came out over thenext 28 days. In the case of the PPBMA deposition with oxygen,the release rate was the slowest and the system released only50% of paclitaxel for 30 days. The release profile seemed tobe a typical Higuchi release pattern [12] (released Mt /M∞=9.52t1 / 2−3.02, R=0.9944), with a continuous release overseveral days. It is clear that the mechanism of paclitaxel releasefrom PPMBA depositionwithout andwith oxygen was different.

For these release systems, which consisted of a rigid barrierlayers and a hydrophobic matrix containing the drug, the drugrelease from the inner matrix coating can be delayed by thebarrier layers. The release rate will vary depending on theformulation variables of the barrier layer (e.g. relative amount ofsoluble/insoluble excipients, coating thickness, surface mor-phology and hydrophilicity) and the release kinetics range fromzero-order to Higuchi's t1 / 2 models [13]. In the case of PPBMAdeposition without oxygen, the apparent release rate was deter-mined by the summation of release rates from the “particulatezone” and the “dense zone” of the plasma PPBMA. The drugrelease from the “particulate zone” was quick and from the“dense zone” was slow, which resulted in a biphasic and irreg-ular patterns release. In the case of PPBMA deposition withoxygen, the slower Higuchi's release might be due to the dense,homogenous and hydrophilic barrier coating.

4. Conclusion

The effects of oxygen on the surface property and controlledrelease characteristics of PPBMAs were investigated. It wasfound that oxygen had little influence on the chemical structureof plasma PPBMAs. A dome-like structure, with nano-sizedparticles, was produced in the case of deposition without oxygenand a smooth and dense surface was produced with oxygen.In the case of deposition with oxygen, the hydrophilicity ofPPBMAwas higher than that without oxygen. Drug release fromPPBMA deposition coating without oxygen showed biphasicpatterns, but the one with oxygen exhibited a slow Higuchirelease.

6864 Y. Yuan et al. / Surface & Coatings Technology 201 (2007) 6861–6864

References

[1] B. Jolanta, I. Gancarz, G. Pozniak, W. Tylus, Eur. Polym. J. 38 (2002) 717.[2] I. Gancarz, G. Pozniak, M. Bryjak, W. Tylus, Eur. Polym. J. 38 (2002)

1937.[3] N. Shirtcliffe, P. Thiemann, M. Stratmann, et al., Surf. Coat. Technol.

142–144 (2001) 1121.[4] X.F. Feng, J. Zhang, H.K. Xie, et al., Surf. Coat. Technol. 171 (2003) 96.[5] M.R. Yang, K.S. Chen, J.L. He, Mater. Chem. Phys. 48 (1997) 71.[6] J.C. Lin, Y.F. Chen, C.Y. Chen, Biomaterials 20 (1999) 1439.

[7] C.S. Kwok, T.A. Horbett, B.D. Ratner, J. Control. Release 62 (1999) 301.[8] S.K. Hendricks, C. Kwok, M.C. Shen, et al., J. Biomed. Mater. Res. 50

(2000) 160.[9] H. Peng, S.Y. Cheng, Z.Q. Fan, J. Appl. Polym. Sci. 92 (2004) 532.[10] I. Gancarz, J. Bryjak, M. Bryjak, et al., Eur. Polym. J. 39 (2003) 1615.[11] M. Kardar, Physica, A 281 (2000) 295.[12] S. Puttipipatkhachorn, J. Nunthanid, K. Yamamoto, J. Control. Release 75

(2001) 143.[13] N. Chidambaram, W. Porter, K. Flood, J. Control. Release 52 (1998) 149.