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Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen
Ceramics International ∎ (∎∎∎∎) ∎∎∎–∎∎∎
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Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen Neda Ghaebi Panah a, Parvin Alizadeh a,n, Bijan Eftekhari Yekta b, Negar Motakef-Kazemi c a Ceramic Group, Department of Materials Science & Engineering, Faculty of Engineering & Technology, Tarbiat Modares University, P. O. Box: 14115-143, Tehran, Iran b Ceramic group, School of Metallurgy and Materials Engineering, Iran University of Science and Technology (IUST), P. O. Box: 16846-13114, Tehran, Iran c Department of Nanochemistry, Faculty of pharmaceutical chemistry, Pharmaceutical sciences branch, Islamic Azad University (IAUPS), Tehran, Iran
art ic l e i nf o
a b s t r a c t
Article history: Received 5 February 2016 Received in revised form 14 March 2016 Accepted 30 March 2016
59SiO2–36CaO–5P2O5 (mol%) as 58S bioactive glass nanotubes were successfully prepared using a coaxial electrospinning process, loaded with Ibuprofen (IBU), and characterized for in-vitro drug release properties. Polyvinylpyrrolidone (PVP) was exploited to manipulate the precursor solutions viscosity. The influence of PVP concentration on fiber formation and its morphology were investigated. The acceptable formation was achieved eventually by dissolving 8 g PVP in 10 ml ethanol. Bioactive glass nanotubes were characterized by field emission scanning electron microscopy (FE-SEM), X-ray powder diffraction (XRD), simultaneous thermal analysis (STA-TG/DTA), nitrogen sorption porosimetry (BET), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), ultraviolet-visible absorption spectroscopy (UV–vis), and energy dispersive spectroscopy analysis (EDS). Accordingly, FT-IR and TG analyses indicated the synthesis of bioactive glass nanotubes has a satisfactory ability to store IBU due to hydrogen bonding between drug and glass. Furthermore, in-vitro drug release tests verified that samples of drug-loaded glass nanotubes were based on Korsmeyer-Peppas model and Fickian diffusion release mechanism. The surface of 58S glass nanotubes was fully crystallized, mostly by hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. & 2016 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
Keywords: Coaxial electrospinning Drug delivery Drug-loaded nanotubes Mesoporous carriers
1. Introduction Electrostatic forces have been used to fabricate fibers for over 100 years in a process called electrospinning whose principles were firstly established by Rayleigh. This technique is able to provide nanofibers with the characteristics of large surface-volume ratio and high porosity. These specifications make nanofibers proper for many applications in biomedical fields such as controlled drug release, tissue engineering, biosensors, and wound dressing. Some parameters which can greatly influence the fiber formation and structure of the generated fibers need optimization such as polymer concentration, feeding rate, applied voltage, and distance from the needle tip [1–4]. Bioactive glass typically possesses biocompatibility, bioactivity, and osteoconductivity which is mainly composed of silicate, calcium oxide, and phosphorus oxide with different relative compositions. Bioactive glass exists in many forms such as bulks, granules, coatings, and fibers; however, there has been a special focus on nanofibers since 2006, when the first fabrication of bioactive n
Corresponding author. E-mail address: [email protected] (P. Alizadeh).
glass nanofibers was reported [1,5]. Coaxial electrospinning technique in fabricating nanotubes might remarkably elevate the bioactivity characteristics. Regarding the apatite layer formed on both outer and inner surfaces of the nanotubes compared to nanofibers, the rate of biomineralization process could be enhanced markedly in nanotubes [1,6]. This layer is responsible for the strong bonding between bioactive glasses and human bone [7]. Considering the bioactivity of silica-based mesoporous materials, a significant development was firstly carried out in 2004. These materials have merits of better bioactive kinetics in comparison to both pure silica mesoporous materials and even sol–gel glasses with similar chemical composition (SiO2–CaO–P2O5). The mesoporous bioactive glass could be a promising research line in the field of bioceramics for bone regeneration. Besides, it might be a substantial factor to take an effective control over the drug release process as a critical issue [8]. The porosity and chemical composition of mesoporous bioactive glasses can heavily influence both loading capacity and kinetics of drug loading [9]. The drug delivery carriers in the context of bone tissue engineering need to fulfill several requirements including biocompatibility, osteoconductivity, and bioresorbability with controllable degradation and resorption rates. Admittedly, bioactive glasses are desirably qualified for these applications [10,11].
http://dx.doi.org/10.1016/j.ceramint.2016.03.228 0272-8842/& 2016 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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The aim of this study is to examine the mesoporous bioactive glass nanotubes fabrication by coaxial electrospinning method and in-vitro characterization of drug-loaded bioactive glass nanotubes with porous surface structure. In order to this purpose, tetraethyl orthosilicate (TEOS), triethyl phosphate (TEP), and calcium nitrate (Ca(NO3)2.4H2O) in the system of 59SiO2–36CaO–5P2O5 (mol%) are used to synthesize mesoporous carriers. After IBU-loading process, in-vitro drug release behavior and kinetics of drug-loaded bioactive glass nanotubes with porous surface structure were investigated.
2. Experimental procedure 2.1. Materials Tetraethyl orthosilicate (TEOS, No. 8.00658), triethyl phosphate (TEP, No. 8.21141), calcium nitrate (Ca(NO3)2.4H2O, No. 1.02121), ethanol (No. 1.00983), HCl (1 mol/L, No. 1.00317), poly(vinylpyrrolidone) (PVP, Mw ¼40,000 g/mol, No. 107443), n-hexane (No. 1.04368), and toluene (No. 1.08323) were supplied by Merck Co. and silicone oil by Acros Organics (No. 163850010). IBU was provided from Jaber Ebne Hayyan pharmaceutical Co. (Tehran, Iran). 2.2. Preparation of spinning solutions The adopted chemical composition of 58S glass is 59SiO2–36CaO–5P2O5 (mol%) chosen based on sol–gel calcium silicate bioglass [12]. The glass precursor solution was prepared by sequentially adding TEOS, TEP, and Ca(NO3)2.4H2O into ethanol and HCl in the volume ratio TEOS:ethanol:HCl ¼1:5:0.05. After stirring for 2 h, 10 ml of this solution was mixed with 10 ml ethanol containing different amounts (4, 5, 6, 7, 8, and 9 g) of PVP that had been stirred for 2 h. Similarly, the mixed solutions required stirring for extra 2 h. In this experiment, the PVP concentration in the solutions was varied from 0.2 to 0.45 g/ml; this factor could have influence on viscosity of the precursor solutions. 2.3. Electrospinning process
Finally, they were washed with n-hexane twice to remove any loosely attached molecules (the excess IBU resided along the surface region) and dried under vacuum at 60 °C for 24 h. These samples of IBU-loaded 58S glass tubes were named IBU-58S. The in-vitro IBU release kinetics was studied in the simulated body fluid (SBF, pH ¼ 7.45). 5 g IBU-58S was immersed in a polypropylene vial with 5 ml SBF (IBU/SBF ¼ 0.1 mg/ml). The vial was incubated in a shaking water bath at the rate of 80 rpm at 37 °C. Different samples (1 ml SBF) were taken from vial to analyse over time intervals, after 0.5, 1, 2, 4, 8, 11.5, 24, and 48 h, then replaced by 1 ml fresh SBF. IBU concentration was determined by ultraviolet–visible absorption spectroscopy (UV–vis). This analysis was carried out to measure the absorbance values at wavelength λ ¼265 nm with the immersing time. All experiments were performed in triplicate. The IBU concentration calibration curve was determined at room temperature by taking absorbance versus IBU SBF solution concentration of 100, 200, 300, 400, and 500 ppm. The UV absorption was measured at wavelength of 265 nm, using a Double Beam OPTIZEN 3220UV UV–vis Spectrophotometer. The calibration curve was in accordance with the Lambert and Beer's law (Eq. 1):
A=0. 003C +0. 008
(1)
where A is the absorbance and C is the concentration (ppm). Typically, the corrected concentration calculation of released IBU could be based on the following equation [13]:
Ctcorr =Ct +
υ V
t−1
∑ Ct 0
(2)
where Ctcorr is the corrected concentration at time t, Ct is the apparent concentration at time t, ν is the volume of sample taken, and V is the total volume of dissolution medium. In order to study the IBU release mechanism from bioactive glass tubes, the in-vitro release data was fitted to KorsmeyerPeppas model [14]. Regarding Korsmeyer-Peppas model, the drug release mechanism often deviates from Fick's law and has an anomalous pattern which can be described by Eq. (3).
Mt /M∞=kt n
(3)
The logarithm form of equation could be written as: The prepared solutions were loaded into a plastic syringe connected to the outer needle (gauge 16). While silicone oil, used as core material, was loaded to another plastic syringe connected to the inner needle (gauge 22). The applied voltage was fixed at 10 kV. A piece of aluminum foil was utilized to collect the ultrafine fibers with a horizontal distance of 8 cm from the needle tip. The feeding rate was adjusted to 0.2 ml/h. All the electrospinning experiments were carried out at room temperature under air ambient using Fanavaran Nano-meghyas Co. electrospinning (Iran). The spun fibers were left at room temperature for 48 h to allow complete TEOS and TEP hydrolysis. In the following step, the aforementioned spun fibers were immersed in toluene for 48 h to remove silicone oil existing in the cores of the fibers; subsequently, dried at room temperature for 24 h. PVP was removed by calcination at 600 °C for 5 h in the air. The heating rate for the calcination was kept at 2 °C/min. 2.4. IBU load and release IBU was selected as the model drug. 0.5 g glass tubes was added into 50 ml IBU n-hexane solution with concentration of 40 mg/ml at room temperature. Consequently, it was immersed for 24 h with magnetic stirring at rate of 100 rpm in a sealed vial to prevent the evaporation of n-hexane. Afterwards, the IBU-loaded 58S glass tubes were separated from solution by centrifugation.
ln (Mt /M∞ ) = ln (k ) + n ln (t )
(4)
where Mt /M∞ is the fractional drug release (F) at time t, k is the kinetic constant, and n is the release exponent which indicates the mechanism of drug transport. For n equal or close to 0.5 there is Fickian diffusion mechanism; however, for n 40.5 the mechanism is anomalous non-Fickian [13,15]. 2.5. Characterization methods The X-ray powder diffraction patterns were examined on a Philips X’pert with Co Kα radiation in the 2θ range of 10–80° at 40 kV and 40 mA. Besides, the structures and morphologies of the glass nanotubes were observed by field emission scanning electron microscopy coupled with an Oxford energy dispersive spectroscopy analysis system in a Zeiss SEM working at 15 kV. The samples were coated with a thin layer of gold before imaging. In addition, Fourier transform infrared spectroscopy analysis was developed on a PerkinElmer Frontier FT-IR spectrometer in the range of 450–4000 cm 1, prepared by mixing the samples with KBr and compaction. Furthermore, simultaneous thermal analysis was performed on a Seiko model SII 6300 with typical sample weight of 12 mg and heating rate of 2 °C/min in the air atmosphere. The curve was acquired in the temperature range of 30– 900 °C. Moreover, thermogravimetric analysis was recorded on an
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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Fig. 1. FE-SEM images of electrospun bioactive glass tubes after immersion in toluene (a, b) and after calcination at 600 °C for 5 h (c, d).
Fig. 3. TGA and DTA curves of 58S tube mat. Fig. 2. XRD patterns of 58S tube mat after elimination silicone oil by solvent (a) and after calcination at 600 °C for 5 h (b).
Thermo Gravimetric Analyzer with Mass Spectrometer, Netzsch TG 209 F1 IRIS at heating rate of 10 °C/min under N2 atmosphere. Finally, nitrogen adsorption–desorption isotherm measurements were accomplished on Micromeritics Gemini 3275 analyzer at 350 °C under a continuous adsorption condition to determine the specific surface area, pore size, and pore volume.
3. Results and discussion 3.1. Preparation, morphologies, and structures of 58S bioactive glass nanotubes Among different PVP concentrations in the solutions from 0.2 to 0.45 g/ml, the solution with 0.4 g/ml concentration achieved by dissolving 8 g PVP in 10 ml ethanol was the best candidate for
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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coaxial electrospinning. In fact, this sample possessed homogeneous structure; not only formed smooth surface without any beads but also had narrower diameter distributions. Generally, the
Fig. 7. Calibration curve for IBU in SBF.
Fig. 4. Nitrogen sorption isotherms of the calcined 58S glass nanotubes.
Fig. 5. FT-IR spectra of IBU (a), IBU-58S (b), and 58S glass nanotubes (c).
Fig. 8. The IBU release behavior from the 58S glass nanotubes.
Fig. 6. TGA curves of IBU-58S (a) and 58S glass nanotubes (b).
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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Fig. 9. The ln(fractional release of IBU) plotted as a function of ln(time) just using the data below 11.5 h.
Table 1 The average values of parameters and the equation of the empirical IBU release model from IBU-58S samples n
k
ln(F) vs. ln(t)
R2
0.474
0.21
Y ¼0.474X-1.559
0.98
5
have smaller average diameter after calcination due to PVP loss. The 58S glass nanotubes' XRD patterns after elimination of silicone oil by solvent and also after calcination at 600 °C for 5 h were depicted in Fig. 2. Both samples, after immersion in solvent and after heating, were amorphous based on the XRD patterns. Additionally, simultaneous thermal analysis was performed on 58S tube mat to determine suitable calcination temperature. TG curve in Fig. 3 shows four mass losses after heating from room temperature to 900 °C. These weight losses appeared at the temperature intervals of 30–100, 100–280, 280–600, and 600–900 °C. The first weight loss was insignificant about 7% (before 100 °C) and can be attributed to the elimination of residual alcohol and adsorbed water. The second obvious loss between 100 and 280 °C can be result of PVP degradation and decomposition of the hydrated salt (elimination of crystallization water). This weight loss step was nearly 73%. The third weight loss at around 280–600 °C might have occurred due to the carbon released by the degradation of both PVP and TEOS and TEP alkoxides, and also decomposition of the nitrate. This weight loss step was nearly 13%. Beyond 600 °C to 900 °C, observed weight loss was negligible (about 1%). Additionally, the white color of tube mat goes to brown by heating which might be due to residual carbon compounds. The sample presents a peak at 280 °C on DTA curve. This peak is perhaps regarded to the degradation of both PVP and alkoxides. The above results confirmed that almost all residuals could be removed up to 600 °C. Therefore, the temperature of 600 °C was chosen as tubes calcination temperature to be high enough to remove organic sources and nitrate but low enough to avoid crystallization. These findings are in accordance to the previous reports and verifiable [6,16]. Fig. 4 shows the nitrogen sorption isotherms of the calcined 58S glass nanotubes. The nitrogen sorption isotherm of the sample is identified as type IV according to IUPAC classification with H1type hysteresis loop, representative of mesoporous materials with cylindrical pores [17,18]. Calcined 58S glass nanotubes at 600 °C for 5 h have pore size of 11.9 nm, BET surface area of 167 m2/g, and pore volume of 0.5 cm3/g. The pore size of calcined 58S glass nanotubes are suitable for the adsorption of IBU molecules (molecule size 1.2 nm 0.6 nm) [19]. 3.2. In-vitro study of drug delivery
Fig. 10. The XRD pattern of IBU-58S after immersion in SBF for 14 days.
viscosity of a solution depends on the polymer concentration in the solvent. The higher concentration of polymer, the greater entanglement of polymer chains. This could be the main factor of forming a smooth surface without any beads. Fig. 1a and b illustrate the FE-SEM images of electrospun bioactive glass tubes/PVP from the final solution with 0.4 g/ml concentration after immersion in toluene for 48 h. In the same way, FE-SEM images were also produced for samples after calcination at 600 °C for 5 h (Fig. 1c and d). Apparently, a rod-like morphology is observed in images with no change in the smooth and continuous structure. The nanotubes
3.2.1. Drug loading The FT-IR spectra for 58S glass nanotubes, IBU-58S, and IBU are illustrated in Fig. 5. As shown in Fig. 5c for the 58S glass nanotubes, the peaks at 489, 799, and 1076 cm 1 can be indexed to Si– O bands and the peak at 604 cm 1 is assigned to the P–O band [20]. The local peaks at 1421 and 1507 cm 1 are seemingly the results of residual carbonic bands [21]. The remarkable absorption bands due to OH at 3427 cm 1 could prove that a great number of –OH groups exist on tubes surface. These –OH groups are essential for IBU molecules chemical bonding. IBU molecules are able to place into pores with or without chemical bonding. As a matter of fact, Si–OH and P–OH groups of the bioactive glass surface play a pivotal role in hydrogen bonding with IBU molecules [10,22]. For the IBU sample in Fig. 5a, the characteristic absorption peaks of – COOH at 1721 cm 1 and benzene ring at 1430-1600 cm 1 of IBU are distinctive in the image. Furthermore, the quaternary carbon atom peaks at 1460 and 1509 cm 1, carboxylate group at 1565 cm 1, and the alkyl group peaks at 2869 and 2957 cm 1 are cleary observed [23,24]. The FT-IR spectra differences of the two samples before and after loaded IBU in Fig. 5c and b confirm the successful adsorption of IBU onto the surface of the mesoporous 58S glass nanotubes. Quantity of IBU loading onto the 58S glass nanotubes was determined by TG analysis. The TG curve of the IBU-58S was shown
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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Fig. 11. FE-SEM images of IBU-58S after immersion in SBF for 24 h (a, b) and 14 days (d, e). EDS analyses of b (c) and e (f).
Table 2 The compositions of silicon, calcium, and phosphorous of 58S glass nanotubes after immersion in SBF for 24 h and 14 days extracted from EDS analysis. Immersion time in SBF
Si wt%
Ca wt%
P wt%
24 h 14supp days
32.1 15.8
23.7 31.5
6.0 15.0
in Fig. 6a. In order to avoid crystallization of 58S glass nanotubes, calcination was performed at 600 °C. Therefore, 58S glass nanotubes can have weight loss from 600 °C to 900 °C due to residual carbon. Fig. 6b depicts the TGA curve of 58S glass nanotubes before loading IBU in the interval 600–900 °C. Thus, the 10% total wight loss observed in Fig. 6a was attributed to both IBU-loaded and glass. In practice, the share of IBU weight loss was about 9%.
The linear calibration curve in the concentration range from 100–500 ppm of IBU is shown in Fig. 7. Obtained Eq. (1) from the calibration curve is A=0.003C +0.008. 3.2.2. In-vitro drug release Fig. 8. illustrates the cumulative IBU release behavior from the 58S glass nanotubes as a function of release time in SBF at 37 °C for 48 h. The drug carrier indicated an initial burst release and a relatively slow subsequent release. The IBU released in the first 0.5 h was around 17 wt% of total IBU amount on average. The release rate decreased over time; however, the average cumulative IBU release from 58S glass nanotubes reached 94.33 wt% during the 48 h. In fact, most of IBU molecules loosely attached on the external surface of glass might easily release during the initial release. On the other hand, IBU molecules hosted into the
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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mesoporous and internal hollow space of tubes typically release through the diffusion over the channel mechanism. In order to study the IBU release mechanism from bioactive glass nanotubes, the in-vitro release data were fitted to Korsmeyer-Peppas model. Since the model of Korsmeyer-Peppas is not applicable beyond 0.6 (F) of the total IBU content, the ln(fractional release of IBU) is plotted as a function of ln(time) just using the data below 11.5 h (Fig. 9) [13]. The parameter n was obtained from the slope of this plot while parameter k was achieved from ln (time ) = 0. Table 1 summarizes the calculated results. In this study, the average value of n is equal to 0.474 which indicates Fickian diffusion release mechanism. Hence, the IBU release behavior could be controlled by diffusion through the channel. 3.3. In-vitro study of bioactivity The XRD pattern of IBU-58S after immersion in SBF for 14 days is shown in Fig. 10. The detected crystalline phases were Hydroxylapatite – Ca8.86(PO4)6(H2O)2 (JCPDS Database No. 01-082-1943) and Tetracalcium phosphate – Ca4(PO4)2O (JCPDS Database No. 01070-1379). The XRD pattern indicates seven characteristic peaks of hydroxylapatite phase at 12.42° (100), 30.08° (002), 36.91° (211), 38.23° (300), 39.67° (202), 53.22° (203), and 78.67° (422). Also, tetracalcium phosphate phase characteristic peaks are observed at ̅ ), 26.14° ( 102 ̅ ), 33.03° (211), ̅ ), 31.81° ( 131 23.37° (012), 25.05° ( 121 47.47° (311), 53.22° (060), 63.42° (261), and 66.55° (154). This result shows that the surface of 58S glass nanotubes was fully crystallized, mostly by hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. The hydroxylapatite phase among the common calcium phosphate phases is the most thermodynamically stable one in SBF physiological environment [7]. The surface morphology and EDS analysis of the IBU-58S after immersion in SBF for 24 h and 14 days are depicted in Fig. 11. FESEM images in Fig. 11a and b demonstrate that the surface morphology of 58S glass nanotubes was not smooth with homogeneous structure as before immersion in SBF. Therefore, the presence of Si–OH groups along the 58S glass nanotube surfaces caused apatite nucleation. Also, some newly formed small deposit areas alongside the tubes were observed as detected by EDS analysis. Calcium and phosphorous concentrations in these areas were slightly more than other surfaces which might be related to the first steps of bioactivity and be due to the ionic exchange. Fig. 11d and e illustrate a significant morphological change compared to the samples before immersion in SBF. The surface of 58S glass nanotubes was fully crystallized, mostly by the nanosphere-like hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. The average size of particles in the hydroxylapatite layer was measured below 50 nm in diameter. The procured results are in agreement with the XRD pattern in which the substantial characteristic peaks of hydroxylapatite phase are obvious after immersion in SBF for 14 days. Apparent changes in both calcium and phosphorous concentrations are detected by comparison of EDS analysis in Fig. 11c and f. The compositions of silicon, calcium, and phosphorous of 58S glass nanotubes after immersion in SBF for 24 h and 14 days extracted from EDS analysis are shown in Table 2. When the immersion time increases, the concentration of silicon reduces whereas both calcium and phosphorous concentrations accrue. Here in this case, 58S glass nanotubes surfaces after immersion in SBF for 14 days showed the Ca/P molar ratio of 1.62, which is close to the stoichiometric ratio of hydroxyapatite (Ca/P E 1.67) [25]. It is notable that Na, Mg, and Cl in the EDS spectrum originate from the SBF.
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4. Conclusions 58S bioactive glass nanotubes with mesoporous structure were successfully synthesized using the coaxial electrospinning process with different polyvinylpyrrolidone concentrations. The acceptable formation was achieved under applied voltage of 10 kV, needle tip distance of 8 cm, feeding rate of 0.2 ml/h, and 0.4 g/ml PVP concentration. As a model drug, IBU storage and release in bioactive glass nanotubes were investigated. With regard to the KorsmeyerPeppas model fitting, the releasing process of drug-loaded glass nanotubes follows the Fickian diffusion release mechanism. Based on the in-vitro characterization, the surface of 58S glass nanotubes was fully crystallized, mostly by hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. Therefore, these results identify that 58S bioactive glass nanotubes as mesoporous carriers are capacious and potentially useful for controlled drug delivery systems.
Acknowledgments Financial and technical supports from Tarbiat Modares University and Iran Nanotechnology Initiative Council, Iran are gratefully acknowledged.
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Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen Neda Ghaebi Panah a, Parvin Alizadeh a,n, Bijan Eftekhari Yekta b, Negar Motakef-Kazemi c a Ceramic Group, Department of Materials Science & Engineering, Faculty of Engineering & Technology, Tarbiat Modares University, P. O. Box: 14115-143, Tehran, Iran b Ceramic group, School of Metallurgy and Materials Engineering, Iran University of Science and Technology (IUST), P. O. Box: 16846-13114, Tehran, Iran c Department of Nanochemistry, Faculty of pharmaceutical chemistry, Pharmaceutical sciences branch, Islamic Azad University (IAUPS), Tehran, Iran
art ic l e i nf o
a b s t r a c t
Article history: Received 5 February 2016 Received in revised form 14 March 2016 Accepted 30 March 2016
59SiO2–36CaO–5P2O5 (mol%) as 58S bioactive glass nanotubes were successfully prepared using a coaxial electrospinning process, loaded with Ibuprofen (IBU), and characterized for in-vitro drug release properties. Polyvinylpyrrolidone (PVP) was exploited to manipulate the precursor solutions viscosity. The influence of PVP concentration on fiber formation and its morphology were investigated. The acceptable formation was achieved eventually by dissolving 8 g PVP in 10 ml ethanol. Bioactive glass nanotubes were characterized by field emission scanning electron microscopy (FE-SEM), X-ray powder diffraction (XRD), simultaneous thermal analysis (STA-TG/DTA), nitrogen sorption porosimetry (BET), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), ultraviolet-visible absorption spectroscopy (UV–vis), and energy dispersive spectroscopy analysis (EDS). Accordingly, FT-IR and TG analyses indicated the synthesis of bioactive glass nanotubes has a satisfactory ability to store IBU due to hydrogen bonding between drug and glass. Furthermore, in-vitro drug release tests verified that samples of drug-loaded glass nanotubes were based on Korsmeyer-Peppas model and Fickian diffusion release mechanism. The surface of 58S glass nanotubes was fully crystallized, mostly by hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. & 2016 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
Keywords: Coaxial electrospinning Drug delivery Drug-loaded nanotubes Mesoporous carriers
1. Introduction Electrostatic forces have been used to fabricate fibers for over 100 years in a process called electrospinning whose principles were firstly established by Rayleigh. This technique is able to provide nanofibers with the characteristics of large surface-volume ratio and high porosity. These specifications make nanofibers proper for many applications in biomedical fields such as controlled drug release, tissue engineering, biosensors, and wound dressing. Some parameters which can greatly influence the fiber formation and structure of the generated fibers need optimization such as polymer concentration, feeding rate, applied voltage, and distance from the needle tip [1–4]. Bioactive glass typically possesses biocompatibility, bioactivity, and osteoconductivity which is mainly composed of silicate, calcium oxide, and phosphorus oxide with different relative compositions. Bioactive glass exists in many forms such as bulks, granules, coatings, and fibers; however, there has been a special focus on nanofibers since 2006, when the first fabrication of bioactive n
Corresponding author. E-mail address: [email protected] (P. Alizadeh).
glass nanofibers was reported [1,5]. Coaxial electrospinning technique in fabricating nanotubes might remarkably elevate the bioactivity characteristics. Regarding the apatite layer formed on both outer and inner surfaces of the nanotubes compared to nanofibers, the rate of biomineralization process could be enhanced markedly in nanotubes [1,6]. This layer is responsible for the strong bonding between bioactive glasses and human bone [7]. Considering the bioactivity of silica-based mesoporous materials, a significant development was firstly carried out in 2004. These materials have merits of better bioactive kinetics in comparison to both pure silica mesoporous materials and even sol–gel glasses with similar chemical composition (SiO2–CaO–P2O5). The mesoporous bioactive glass could be a promising research line in the field of bioceramics for bone regeneration. Besides, it might be a substantial factor to take an effective control over the drug release process as a critical issue [8]. The porosity and chemical composition of mesoporous bioactive glasses can heavily influence both loading capacity and kinetics of drug loading [9]. The drug delivery carriers in the context of bone tissue engineering need to fulfill several requirements including biocompatibility, osteoconductivity, and bioresorbability with controllable degradation and resorption rates. Admittedly, bioactive glasses are desirably qualified for these applications [10,11].
http://dx.doi.org/10.1016/j.ceramint.2016.03.228 0272-8842/& 2016 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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The aim of this study is to examine the mesoporous bioactive glass nanotubes fabrication by coaxial electrospinning method and in-vitro characterization of drug-loaded bioactive glass nanotubes with porous surface structure. In order to this purpose, tetraethyl orthosilicate (TEOS), triethyl phosphate (TEP), and calcium nitrate (Ca(NO3)2.4H2O) in the system of 59SiO2–36CaO–5P2O5 (mol%) are used to synthesize mesoporous carriers. After IBU-loading process, in-vitro drug release behavior and kinetics of drug-loaded bioactive glass nanotubes with porous surface structure were investigated.
2. Experimental procedure 2.1. Materials Tetraethyl orthosilicate (TEOS, No. 8.00658), triethyl phosphate (TEP, No. 8.21141), calcium nitrate (Ca(NO3)2.4H2O, No. 1.02121), ethanol (No. 1.00983), HCl (1 mol/L, No. 1.00317), poly(vinylpyrrolidone) (PVP, Mw ¼40,000 g/mol, No. 107443), n-hexane (No. 1.04368), and toluene (No. 1.08323) were supplied by Merck Co. and silicone oil by Acros Organics (No. 163850010). IBU was provided from Jaber Ebne Hayyan pharmaceutical Co. (Tehran, Iran). 2.2. Preparation of spinning solutions The adopted chemical composition of 58S glass is 59SiO2–36CaO–5P2O5 (mol%) chosen based on sol–gel calcium silicate bioglass [12]. The glass precursor solution was prepared by sequentially adding TEOS, TEP, and Ca(NO3)2.4H2O into ethanol and HCl in the volume ratio TEOS:ethanol:HCl ¼1:5:0.05. After stirring for 2 h, 10 ml of this solution was mixed with 10 ml ethanol containing different amounts (4, 5, 6, 7, 8, and 9 g) of PVP that had been stirred for 2 h. Similarly, the mixed solutions required stirring for extra 2 h. In this experiment, the PVP concentration in the solutions was varied from 0.2 to 0.45 g/ml; this factor could have influence on viscosity of the precursor solutions. 2.3. Electrospinning process
Finally, they were washed with n-hexane twice to remove any loosely attached molecules (the excess IBU resided along the surface region) and dried under vacuum at 60 °C for 24 h. These samples of IBU-loaded 58S glass tubes were named IBU-58S. The in-vitro IBU release kinetics was studied in the simulated body fluid (SBF, pH ¼ 7.45). 5 g IBU-58S was immersed in a polypropylene vial with 5 ml SBF (IBU/SBF ¼ 0.1 mg/ml). The vial was incubated in a shaking water bath at the rate of 80 rpm at 37 °C. Different samples (1 ml SBF) were taken from vial to analyse over time intervals, after 0.5, 1, 2, 4, 8, 11.5, 24, and 48 h, then replaced by 1 ml fresh SBF. IBU concentration was determined by ultraviolet–visible absorption spectroscopy (UV–vis). This analysis was carried out to measure the absorbance values at wavelength λ ¼265 nm with the immersing time. All experiments were performed in triplicate. The IBU concentration calibration curve was determined at room temperature by taking absorbance versus IBU SBF solution concentration of 100, 200, 300, 400, and 500 ppm. The UV absorption was measured at wavelength of 265 nm, using a Double Beam OPTIZEN 3220UV UV–vis Spectrophotometer. The calibration curve was in accordance with the Lambert and Beer's law (Eq. 1):
A=0. 003C +0. 008
(1)
where A is the absorbance and C is the concentration (ppm). Typically, the corrected concentration calculation of released IBU could be based on the following equation [13]:
Ctcorr =Ct +
υ V
t−1
∑ Ct 0
(2)
where Ctcorr is the corrected concentration at time t, Ct is the apparent concentration at time t, ν is the volume of sample taken, and V is the total volume of dissolution medium. In order to study the IBU release mechanism from bioactive glass tubes, the in-vitro release data was fitted to KorsmeyerPeppas model [14]. Regarding Korsmeyer-Peppas model, the drug release mechanism often deviates from Fick's law and has an anomalous pattern which can be described by Eq. (3).
Mt /M∞=kt n
(3)
The logarithm form of equation could be written as: The prepared solutions were loaded into a plastic syringe connected to the outer needle (gauge 16). While silicone oil, used as core material, was loaded to another plastic syringe connected to the inner needle (gauge 22). The applied voltage was fixed at 10 kV. A piece of aluminum foil was utilized to collect the ultrafine fibers with a horizontal distance of 8 cm from the needle tip. The feeding rate was adjusted to 0.2 ml/h. All the electrospinning experiments were carried out at room temperature under air ambient using Fanavaran Nano-meghyas Co. electrospinning (Iran). The spun fibers were left at room temperature for 48 h to allow complete TEOS and TEP hydrolysis. In the following step, the aforementioned spun fibers were immersed in toluene for 48 h to remove silicone oil existing in the cores of the fibers; subsequently, dried at room temperature for 24 h. PVP was removed by calcination at 600 °C for 5 h in the air. The heating rate for the calcination was kept at 2 °C/min. 2.4. IBU load and release IBU was selected as the model drug. 0.5 g glass tubes was added into 50 ml IBU n-hexane solution with concentration of 40 mg/ml at room temperature. Consequently, it was immersed for 24 h with magnetic stirring at rate of 100 rpm in a sealed vial to prevent the evaporation of n-hexane. Afterwards, the IBU-loaded 58S glass tubes were separated from solution by centrifugation.
ln (Mt /M∞ ) = ln (k ) + n ln (t )
(4)
where Mt /M∞ is the fractional drug release (F) at time t, k is the kinetic constant, and n is the release exponent which indicates the mechanism of drug transport. For n equal or close to 0.5 there is Fickian diffusion mechanism; however, for n 40.5 the mechanism is anomalous non-Fickian [13,15]. 2.5. Characterization methods The X-ray powder diffraction patterns were examined on a Philips X’pert with Co Kα radiation in the 2θ range of 10–80° at 40 kV and 40 mA. Besides, the structures and morphologies of the glass nanotubes were observed by field emission scanning electron microscopy coupled with an Oxford energy dispersive spectroscopy analysis system in a Zeiss SEM working at 15 kV. The samples were coated with a thin layer of gold before imaging. In addition, Fourier transform infrared spectroscopy analysis was developed on a PerkinElmer Frontier FT-IR spectrometer in the range of 450–4000 cm 1, prepared by mixing the samples with KBr and compaction. Furthermore, simultaneous thermal analysis was performed on a Seiko model SII 6300 with typical sample weight of 12 mg and heating rate of 2 °C/min in the air atmosphere. The curve was acquired in the temperature range of 30– 900 °C. Moreover, thermogravimetric analysis was recorded on an
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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Fig. 1. FE-SEM images of electrospun bioactive glass tubes after immersion in toluene (a, b) and after calcination at 600 °C for 5 h (c, d).
Fig. 3. TGA and DTA curves of 58S tube mat. Fig. 2. XRD patterns of 58S tube mat after elimination silicone oil by solvent (a) and after calcination at 600 °C for 5 h (b).
Thermo Gravimetric Analyzer with Mass Spectrometer, Netzsch TG 209 F1 IRIS at heating rate of 10 °C/min under N2 atmosphere. Finally, nitrogen adsorption–desorption isotherm measurements were accomplished on Micromeritics Gemini 3275 analyzer at 350 °C under a continuous adsorption condition to determine the specific surface area, pore size, and pore volume.
3. Results and discussion 3.1. Preparation, morphologies, and structures of 58S bioactive glass nanotubes Among different PVP concentrations in the solutions from 0.2 to 0.45 g/ml, the solution with 0.4 g/ml concentration achieved by dissolving 8 g PVP in 10 ml ethanol was the best candidate for
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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coaxial electrospinning. In fact, this sample possessed homogeneous structure; not only formed smooth surface without any beads but also had narrower diameter distributions. Generally, the
Fig. 7. Calibration curve for IBU in SBF.
Fig. 4. Nitrogen sorption isotherms of the calcined 58S glass nanotubes.
Fig. 5. FT-IR spectra of IBU (a), IBU-58S (b), and 58S glass nanotubes (c).
Fig. 8. The IBU release behavior from the 58S glass nanotubes.
Fig. 6. TGA curves of IBU-58S (a) and 58S glass nanotubes (b).
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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Fig. 9. The ln(fractional release of IBU) plotted as a function of ln(time) just using the data below 11.5 h.
Table 1 The average values of parameters and the equation of the empirical IBU release model from IBU-58S samples n
k
ln(F) vs. ln(t)
R2
0.474
0.21
Y ¼0.474X-1.559
0.98
5
have smaller average diameter after calcination due to PVP loss. The 58S glass nanotubes' XRD patterns after elimination of silicone oil by solvent and also after calcination at 600 °C for 5 h were depicted in Fig. 2. Both samples, after immersion in solvent and after heating, were amorphous based on the XRD patterns. Additionally, simultaneous thermal analysis was performed on 58S tube mat to determine suitable calcination temperature. TG curve in Fig. 3 shows four mass losses after heating from room temperature to 900 °C. These weight losses appeared at the temperature intervals of 30–100, 100–280, 280–600, and 600–900 °C. The first weight loss was insignificant about 7% (before 100 °C) and can be attributed to the elimination of residual alcohol and adsorbed water. The second obvious loss between 100 and 280 °C can be result of PVP degradation and decomposition of the hydrated salt (elimination of crystallization water). This weight loss step was nearly 73%. The third weight loss at around 280–600 °C might have occurred due to the carbon released by the degradation of both PVP and TEOS and TEP alkoxides, and also decomposition of the nitrate. This weight loss step was nearly 13%. Beyond 600 °C to 900 °C, observed weight loss was negligible (about 1%). Additionally, the white color of tube mat goes to brown by heating which might be due to residual carbon compounds. The sample presents a peak at 280 °C on DTA curve. This peak is perhaps regarded to the degradation of both PVP and alkoxides. The above results confirmed that almost all residuals could be removed up to 600 °C. Therefore, the temperature of 600 °C was chosen as tubes calcination temperature to be high enough to remove organic sources and nitrate but low enough to avoid crystallization. These findings are in accordance to the previous reports and verifiable [6,16]. Fig. 4 shows the nitrogen sorption isotherms of the calcined 58S glass nanotubes. The nitrogen sorption isotherm of the sample is identified as type IV according to IUPAC classification with H1type hysteresis loop, representative of mesoporous materials with cylindrical pores [17,18]. Calcined 58S glass nanotubes at 600 °C for 5 h have pore size of 11.9 nm, BET surface area of 167 m2/g, and pore volume of 0.5 cm3/g. The pore size of calcined 58S glass nanotubes are suitable for the adsorption of IBU molecules (molecule size 1.2 nm 0.6 nm) [19]. 3.2. In-vitro study of drug delivery
Fig. 10. The XRD pattern of IBU-58S after immersion in SBF for 14 days.
viscosity of a solution depends on the polymer concentration in the solvent. The higher concentration of polymer, the greater entanglement of polymer chains. This could be the main factor of forming a smooth surface without any beads. Fig. 1a and b illustrate the FE-SEM images of electrospun bioactive glass tubes/PVP from the final solution with 0.4 g/ml concentration after immersion in toluene for 48 h. In the same way, FE-SEM images were also produced for samples after calcination at 600 °C for 5 h (Fig. 1c and d). Apparently, a rod-like morphology is observed in images with no change in the smooth and continuous structure. The nanotubes
3.2.1. Drug loading The FT-IR spectra for 58S glass nanotubes, IBU-58S, and IBU are illustrated in Fig. 5. As shown in Fig. 5c for the 58S glass nanotubes, the peaks at 489, 799, and 1076 cm 1 can be indexed to Si– O bands and the peak at 604 cm 1 is assigned to the P–O band [20]. The local peaks at 1421 and 1507 cm 1 are seemingly the results of residual carbonic bands [21]. The remarkable absorption bands due to OH at 3427 cm 1 could prove that a great number of –OH groups exist on tubes surface. These –OH groups are essential for IBU molecules chemical bonding. IBU molecules are able to place into pores with or without chemical bonding. As a matter of fact, Si–OH and P–OH groups of the bioactive glass surface play a pivotal role in hydrogen bonding with IBU molecules [10,22]. For the IBU sample in Fig. 5a, the characteristic absorption peaks of – COOH at 1721 cm 1 and benzene ring at 1430-1600 cm 1 of IBU are distinctive in the image. Furthermore, the quaternary carbon atom peaks at 1460 and 1509 cm 1, carboxylate group at 1565 cm 1, and the alkyl group peaks at 2869 and 2957 cm 1 are cleary observed [23,24]. The FT-IR spectra differences of the two samples before and after loaded IBU in Fig. 5c and b confirm the successful adsorption of IBU onto the surface of the mesoporous 58S glass nanotubes. Quantity of IBU loading onto the 58S glass nanotubes was determined by TG analysis. The TG curve of the IBU-58S was shown
Please cite this article as: N. Ghaebi Panah, et al., Preparation and in-vitro characterization of electrospun bioactive glass nanotubes as mesoporous carriers for ibuprofen, Ceramics International (2016), http://dx.doi.org/10.1016/j.ceramint.2016.03.228i
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Fig. 11. FE-SEM images of IBU-58S after immersion in SBF for 24 h (a, b) and 14 days (d, e). EDS analyses of b (c) and e (f).
Table 2 The compositions of silicon, calcium, and phosphorous of 58S glass nanotubes after immersion in SBF for 24 h and 14 days extracted from EDS analysis. Immersion time in SBF
Si wt%
Ca wt%
P wt%
24 h 14supp days
32.1 15.8
23.7 31.5
6.0 15.0
in Fig. 6a. In order to avoid crystallization of 58S glass nanotubes, calcination was performed at 600 °C. Therefore, 58S glass nanotubes can have weight loss from 600 °C to 900 °C due to residual carbon. Fig. 6b depicts the TGA curve of 58S glass nanotubes before loading IBU in the interval 600–900 °C. Thus, the 10% total wight loss observed in Fig. 6a was attributed to both IBU-loaded and glass. In practice, the share of IBU weight loss was about 9%.
The linear calibration curve in the concentration range from 100–500 ppm of IBU is shown in Fig. 7. Obtained Eq. (1) from the calibration curve is A=0.003C +0.008. 3.2.2. In-vitro drug release Fig. 8. illustrates the cumulative IBU release behavior from the 58S glass nanotubes as a function of release time in SBF at 37 °C for 48 h. The drug carrier indicated an initial burst release and a relatively slow subsequent release. The IBU released in the first 0.5 h was around 17 wt% of total IBU amount on average. The release rate decreased over time; however, the average cumulative IBU release from 58S glass nanotubes reached 94.33 wt% during the 48 h. In fact, most of IBU molecules loosely attached on the external surface of glass might easily release during the initial release. On the other hand, IBU molecules hosted into the
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mesoporous and internal hollow space of tubes typically release through the diffusion over the channel mechanism. In order to study the IBU release mechanism from bioactive glass nanotubes, the in-vitro release data were fitted to Korsmeyer-Peppas model. Since the model of Korsmeyer-Peppas is not applicable beyond 0.6 (F) of the total IBU content, the ln(fractional release of IBU) is plotted as a function of ln(time) just using the data below 11.5 h (Fig. 9) [13]. The parameter n was obtained from the slope of this plot while parameter k was achieved from ln (time ) = 0. Table 1 summarizes the calculated results. In this study, the average value of n is equal to 0.474 which indicates Fickian diffusion release mechanism. Hence, the IBU release behavior could be controlled by diffusion through the channel. 3.3. In-vitro study of bioactivity The XRD pattern of IBU-58S after immersion in SBF for 14 days is shown in Fig. 10. The detected crystalline phases were Hydroxylapatite – Ca8.86(PO4)6(H2O)2 (JCPDS Database No. 01-082-1943) and Tetracalcium phosphate – Ca4(PO4)2O (JCPDS Database No. 01070-1379). The XRD pattern indicates seven characteristic peaks of hydroxylapatite phase at 12.42° (100), 30.08° (002), 36.91° (211), 38.23° (300), 39.67° (202), 53.22° (203), and 78.67° (422). Also, tetracalcium phosphate phase characteristic peaks are observed at ̅ ), 26.14° ( 102 ̅ ), 33.03° (211), ̅ ), 31.81° ( 131 23.37° (012), 25.05° ( 121 47.47° (311), 53.22° (060), 63.42° (261), and 66.55° (154). This result shows that the surface of 58S glass nanotubes was fully crystallized, mostly by hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. The hydroxylapatite phase among the common calcium phosphate phases is the most thermodynamically stable one in SBF physiological environment [7]. The surface morphology and EDS analysis of the IBU-58S after immersion in SBF for 24 h and 14 days are depicted in Fig. 11. FESEM images in Fig. 11a and b demonstrate that the surface morphology of 58S glass nanotubes was not smooth with homogeneous structure as before immersion in SBF. Therefore, the presence of Si–OH groups along the 58S glass nanotube surfaces caused apatite nucleation. Also, some newly formed small deposit areas alongside the tubes were observed as detected by EDS analysis. Calcium and phosphorous concentrations in these areas were slightly more than other surfaces which might be related to the first steps of bioactivity and be due to the ionic exchange. Fig. 11d and e illustrate a significant morphological change compared to the samples before immersion in SBF. The surface of 58S glass nanotubes was fully crystallized, mostly by the nanosphere-like hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. The average size of particles in the hydroxylapatite layer was measured below 50 nm in diameter. The procured results are in agreement with the XRD pattern in which the substantial characteristic peaks of hydroxylapatite phase are obvious after immersion in SBF for 14 days. Apparent changes in both calcium and phosphorous concentrations are detected by comparison of EDS analysis in Fig. 11c and f. The compositions of silicon, calcium, and phosphorous of 58S glass nanotubes after immersion in SBF for 24 h and 14 days extracted from EDS analysis are shown in Table 2. When the immersion time increases, the concentration of silicon reduces whereas both calcium and phosphorous concentrations accrue. Here in this case, 58S glass nanotubes surfaces after immersion in SBF for 14 days showed the Ca/P molar ratio of 1.62, which is close to the stoichiometric ratio of hydroxyapatite (Ca/P E 1.67) [25]. It is notable that Na, Mg, and Cl in the EDS spectrum originate from the SBF.
7
4. Conclusions 58S bioactive glass nanotubes with mesoporous structure were successfully synthesized using the coaxial electrospinning process with different polyvinylpyrrolidone concentrations. The acceptable formation was achieved under applied voltage of 10 kV, needle tip distance of 8 cm, feeding rate of 0.2 ml/h, and 0.4 g/ml PVP concentration. As a model drug, IBU storage and release in bioactive glass nanotubes were investigated. With regard to the KorsmeyerPeppas model fitting, the releasing process of drug-loaded glass nanotubes follows the Fickian diffusion release mechanism. Based on the in-vitro characterization, the surface of 58S glass nanotubes was fully crystallized, mostly by hydroxylapatite phase and partially by tetracalcium phosphate layer after immersion in SBF for 14 days. Therefore, these results identify that 58S bioactive glass nanotubes as mesoporous carriers are capacious and potentially useful for controlled drug delivery systems.
Acknowledgments Financial and technical supports from Tarbiat Modares University and Iran Nanotechnology Initiative Council, Iran are gratefully acknowledged.
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