Bio-Medical Materials and Engineering 24 (2014) 1269–1274 DOI 10.3233/BME-130929 IOS Press

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Preparation and characterization of silicone rubber/nano-copper nanocomposites for use in intrauterine devices Yongjun Chen*, Yuanfang Luo, Zhixin Jia, Demin Jia and Juan Chen Department of Polymer Materials and Engineering, South China University of Technology, Wushan Road,Tianhe District, Guangzhou, China

Abstract. In this work, a novel silicone rubber/nano-copper nanocomposite for use in intrauterine devices (IUDs) was developed. Moreover, the release rate of Cu2+ ions and the water absorption of the prepared nanocomposite were investigated in detail. The results indicate that the release rate of Cu2+ ions and water absorption capability of the silicone rubber/nanocopper nanocomposite increase as the nano-copper content increases. SEM analysis suggested there is a uniform dispersion of nano-copper in the silicone matrix. Further, systematic analysis indicated that the release rate of Cu2+ions in the prepared nanocomposite-based IUD can be stabilized for months, which is not possible in the case of traditional IUDs. Keywords: silicone rubber, nano-copper, nanocomposites, intrauterine devices

1. Introduction According to the United Nations, the world population exceeded 7 billion in 2011. It is speculated that the population will exceed 9 billion by the year 2050. One efficient way to control this drastic increase in population is to promote the use of safe contraceptive methods for adult women [1,2]. Women around the world are currently using several contraceptive methods. Among them, intrauterine devices (IUDs), which can release Cu2+ ions invivo, is an effective and easy contraceptive method. However, postpartum IUD insertion increases the risk of complications induced by a burst release of Cu2+ ions, and such problems include perforation, pain, and bleeding. The excess release of Cu2+ ions in turn causes cytotoxic effects [3–6]. Due to this issue, polymer matrix composites have been developed to decrease the drawbacks of conventional Cu-IUD materials. The polymer composite-based IUDs offer the advantage of controlled release of Cu2+ ions [7–10], thereby reducing drastic side effects. Silicone rubbers (SR) have been widely used for numerous biomedical applications due to their excellent mechanical properties and biocompatibility [11-12]. In this paper, novel silicone rubber (SR)/nano-copper (NC) nanocomposites were prepared and their suitability as a new class of IUD material was investigated. Silicone rubber was chosen as the matrix and nano-copper was used as the functional filler. Detailed analysis of the Cu2+ ion release behavior from the nanocomposites indicated *

Corresponding author. E-mail: [email protected].

0959-2989/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved

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that the prepared silicone rubber (SR)/nano-copper (NC) nanocomposites had stable Cu2+ ion release behavior due to the combined effect of nano structuring and hydrophilicity modification. Compared to traditional IUDs, the silicone rubber/nano-copper nanocomposites prepared in this study eliminated the burst release of the Cu2+ ions and also achieved sustainable release of the ions. 2. Materials and methods 2.1. Materials and instruments 50 nm nano-copper particles were obtained from the Shanghai Super Wei Nami Technology Co., Ltd., China. Silicone rubber (Silastic® Q7-4535 Biomedical grade ETR elastomer) was obtained from Dow Corning, USA. Anhydrous calcium chloride (CaCl2), 1,4-butanediol, glucose, sodium bicarbonate (NaHCO3), and sodium phosphate monobasic dihydrate (NaH2PO4•2H2O) were obtained from the Tianjin Fu Chen Chemical Reagent Factory, China and used without further purification. Commercially used TCu220C and Cu375IUD were obtained from the Yantai Family Planning Medicine & Apparatus Co., Ltd, China. The UV/V is absorbance was measured by a UV spectrophotometer (UV-4802, Unico Shanghai Instruments Co., Ltd., China) at 266 nm. The morphologies of the fracture surfaces in the tensile specimens were observed with a JEOL-6380scanning electron microscope

(SEM) at an accelerating voltage of 15.0 kV. The specimen’s fracture surfaces were sputtercoated with gold prior to their observation. The contact angles of the composites were measured using a DSA100drop shape analysis system (Krüss GmbH, Germany). Fourier transform infrared analysis was performed using a VERTEX 70 FTIR spectrometer (Bruker Optics, Inc., Germany) with an ATR accessory. 2.2. Preparation of SR/nano-copper nanocomposites The composites were prepared using a two-roll laboratory model open mixing mill (length 600 mm × diameter 230 mm). The total mixing time was about 30 min, including 5 min for mixing the nanocopper. The refolded sheet was cut into cylinders that were10 mm thick and had 30 mm diameters. Subsequently, the cylinders were vulcanized in a mold at 160°C at a pressure of 10 MPa for 15 min. The secondary vulcanization was carried out at 180°C for 2 h in an air flow drier. 2.3. Measurement of Cu2+ions released in simulated uterine solutions The copper release rate in a simulated uterine solution was determined from the absorbance measurements based on a procedure previously reported in the literature [13]. The composition of the simulated uterine solution is shown in Table 1. The pH value of the uterine solution was periodically monitored throughout the exposure time, and it was maintained at 6.3 by adding dilute hydrochloric acid or sodium hydroxide solution. For analysis, three 5.0 × 5.0 × 0.1 cm specimens were cut from the cylinder composite, and they were suspended in 50ml of the simulated uterine solution at 37.0 ± 0.1°C. The amount of Cu2+ions released in the uterine solution was determined using an UV/V is double beam spectrophotometer. The samples were analyzed once per week for three months.

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Table 1 Composition of simulated uterine solution Concentration in water (g/L) NaHCO3 NaH2PO4·2H2O 0.25 0.072

Glucose 0.50

CaCl2 0.167

KCl 0.224

NaCl 4.97

2.4. Water sorption The masses of each specimen were initially recorded (m1). The specimens were randomly placed in 10 mL of de-ionized water held at 37 ± 1°C in individual glass vials. At different time points, each specimen was carefully dried by filter paper, weighed to ±0.01 mg, and returned to fresh water storage. The recorded mass was noted (m2(t)). The percentage of apparent mass change during water sorption (Ms(%)) was calculated by:

Ms (%) =

m2 (t ) − m1 × 100 m1

3. Results and discussion 3.1. Water sorption of nanocomposites Figure 1 illustrates the water absorption of silicone rubber (SR)/nano-copper nanocomposites with different contents of nano-copper for the first eight weeks. As evidenced from the plot, as the nanocopper content increases the water absorption of the nanocomposites increases at a faster rate in the initial two weeks and then gradually tends to saturate in the later weeks. This trend could be explained based on how water molecules enter the reticular structure. As the water molecules penetrate the structure, the crosslinking chain segments of the silicone rubber reticular structure become elongated, resulting in a high elastic strain. When the seepage pressure becomes equal to the internal stress of the reticular structure, water absorption ceases and dynamic equilibrium is achieved.

Figure 1 Water sorption of SR/nano-copper nanocomposites with different nano-copper contents

3.2. Cu2+ions release rate of the SR/nano-copper nanocomposites Figure 2 demonstrates the Cu2+ ion release rate of SR/Cu-40 and of the commercial intrauterine devices (IUD), namely, TCu220C and Cu375IUD. As clearly seen from the figure, TCu220C and

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Cu375IUD have high release rates in the first month. In other words, an initial burst could be observed in both the commercial IUDs. This is due to fact that the commercial IUDs are made of bare Cu materials, such as Cu pipe or Cu wire, which have large surface areas. When these materials come into direct contact with uterine fluid, the copper ions are released faster. But after this initial burst, the IUDs tend to saturate gradually. Typically, the release rate of Cu375IUD remained at around 180 µg per day, while that of TCu220C was around 100 µg per day. Intriguingly, it could be observed that the Cu2+ ions release rate of the SR/Cu-40 prepared in this study was significantly lower than those of both TCu220C and Cu375IUD, especially in the earlier stages. Even in the later stages, the release rate constantly stayed at around 25 µg per day. However, the overall release process was found to be quite stable. The mechanism underlying the release of copper ions from nanocomposite could be explained as follows. First, the external uterine solution enters the nanocomposite via the holes in the sample. This sets up a concentration gradient of Cu2+ ions between the inside and outside of the sample. Due to this concentration gradient, the Cu2+ ions start to diffuse into the external solution. The copper ions diffuse through the polymer matrix by threading through the amorphous area of the polymer or by traveling through the holes inside the polymer. The diffusion rate of copper ions in the polymer matrix is lower than in solution. Moreover, as the diffusion occurs further inside the sample, the contact area between the nano-Cu particles and solution is gradually reduced. So, the release rate of copper ions decreases accordingly. Thus, the release of copper ions from the composite is a slow-release process. Therefore, compared with commercial IUDs, the SR/nano-copper nanocomposite can more effectively solve the problem of initial Cu2+ ion burst that is a problem in traditional IUDs. Moreover, this new material can achieve the constant and stable release of copper ions. However, this kind of cupric ion controlled release system, which also has a compact structure, is difficult to control with respect to its cupric ions release rate when a large proportion of copper particles is utilized [13-15].

Figure 2 Cu2+ion release rate of TCu220C, Cu375IUD, and SR/Cu-40 nanocomposites

Figure 3 shows the Cu2+ ion release rate of nanocomposites with different nano-copper contents. The figure shows that the Cu2+ ion release rate in all samples is higher in the initial stage, and then becomes steady in the later release period. The early fast release can be attributed to the nano-copper particle distribution on the sample surface. These particles directly contact and react with the simulated UF, resulting in the fast formation of copper ions, as discussed earlier. The copper ions generated in this manner directly enter into the simulated uterine solution. This is the reason for the observed steep increase in the release of Cu2+ ions in the initial stage. As evidenced from the plot shown in Figure 3, the

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amount of Cu2+ ions released in the system increases as the content of nano-copper particles in the composite increases. This can be explained based on the fact that, as the content of nano-copper in the composite increases, the quantity of nano-copper particles in the diffusion channels increases correspondingly. Consequently, the rate of diffusion of the simulated uterine solution into the sample is accelerated. This further leads to a higher diffusion rate of the nano-copper particles, thereby enhancing the release rate of Cu2+ ions.

Figure 3 Effect of nano-copper content on Cu2+ ion release rate

Figure 4 SEM images of SR/nano-copper composites with different nano-copper contents: (a) 5%, (b) 10%, (c) 20%, (d) 40%

3.3. Morphology of the SR/nano-copper nanocomposites Figures 4(a)–(d) show the SEM images of the SR/nano-copper nanocomposites containing 5 wt%, 10 wt%, 15 wt% and 40 wt% nano-copper, respectively. As evidenced from the SEM image, most of the copper particles are dispersed homogeneously in the polymer matrix. In addition, the surface mor-

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phology of the samples indicated the formation of few aggregated copper particles, although the size of such aggregates was found to be rather small. 4. Conclusions Silicone rubber (SR)/nano-copper nanocomposites were successfully prepared and their suitability for use in IUDs was investigated. Morphological analysis confirmed the uniform distribution of nanocopper in the SR matrix. Comparison of the Cu2+ ions release rate of commercial IUDs and the nanocomposite-based IUD revealed that the burst release of Cu2+ ions can be eliminated and Cu2+ ions can be released in a stable manner for months in the case of nanocomposite-based IUDs. These results imply that IUDs based on the SR/nano-copper nanocomposites prepared in this study can potentially replace traditional IUDs. 5. Acknowledgment The authors thank the Fundamental Research for the Joint Funds of the National Natural Science Foundation of China U1134005 and the Central Universities 2012ZM0009 for financial supports. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]

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nano-copper nanocomposites for use in intrauterine devices.

In this work, a novel silicone rubber/nano-copper nanocomposite for use in intrauterine devices (IUDs) was developed. Moreover, the release rate of Cu...
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