Synthesis of CaTiO3 nanofibers with controllable drug-release kinetics

Article abstract of DOI:10.1002/ejic.201500737

Calcium titanate (CaTiO₃) nanofibers with controlled micro-structure were fabricated by a combination of sol–gel and electrospinning approaches. The fiber morphology has been found to rely significantly on the precursor composition. Altering the volume ratio of ethanol to acetic acid from 3.5 to 1.25 enables the morphology of the CaTiO₃ nanofibers to be transformed from fibers with a circular cross section to curved ribbon-like structures. Ibuprofen (IBU) was used as a model drug to investigate the drug-loading capacity and drug-release profile of the nanofibers. It was found that the BET surface area and the pore volume decrease markedly with the utilization of F127 surfactant. The nanofibers synthesized without F127 surfactant present the highest drug-loading capacity and the most sustained release kinetics. This study suggests that calcium titanate nanofibers can offer a promising platform for localized drug delivery.

Full text of DOI:10.1002/ejic.201500737

FULL PAPER
CLUSTER
ISSUE
DOI:10.1002/ejic.201500737
Synthesis of CaTiO3 Nanofibers with Controllable Drug-
Release Kinetics
Qiuhong Zhang,[a] Xiang Li,*[a] Zhaohui Ren,[a] Gaorong Han,*[a]
and Chuanbin Mao*[a,b]
BACK COVER
Keywords: Sol–gel processes / Surfactants / Nanofibers / Electrospinning / Drug delivery
Calcium titanate (CaTiO3) nanofibers with controlled micro-
structure were fabricated by a combination of sol–gel and
electrospinning approaches. The fiber morphology has been
found to rely significantly on the precursor composition. Al-
tering the volume ratio of ethanol to acetic acid from 3.5 to
1.25 enables the morphology of the CaTiO3 nanofibers to be
transformed from fibers with a circular cross section to
curved ribbon-like structures. Ibuprofen (IBU) was used as a
model drug to investigate the drug-loading capacity and
drug-release profile of the nanofibers. It was found that the
BET surface area and the pore volume decrease markedly
with the utilization of F127 surfactant. The nanofibers syn-
thesized without F127 surfactant present the highest drug-
loading capacity and the most sustained release kinetics.
This study suggests that calcium titanate nanofibers can offer
a promising platform for localized drug delivery.
bility and identified biocompatibility of CaTiO3 make it
possible to extend its applications in localized drug delivery.
To date, much effort has been devoted to the synthesis of
CaTiO3 micro-/nanostructures by methods such as a
PEG-200-assisted solvothermal procedure,[8] the sol–gel
method,[9] and hydrothermal methods.[10]
Introduction
Research on localized drug-delivery systems (LDDSs)
have received burgeoning attention and have advanced
rapidly in the last years due to their great potential to im-
prove human health. Compared with conventional forms
of drug dosage, LDDSs display many advantages including
greater efficacy and safety, controlled and prolonged release
time, and predictable therapeutic response.[1] More recently,
on the basis of the large surface area of nanofibers, the
sustained drug-release kinetics, and the nontoxic nature of
inorganic materials, inorganic nanofibers such as silica,[2]
bioactive glass,[3] and hydroxyapatite[4] have been widely in-
vestigated as candidates for modern LDDSs.
Calcium titanate (CaTiO3) is a well-known bioceramic.
It has been extensively used for orthopedic implants as a
coating material.[5] A CaTiO3 coating layer between tita-
nium substrate and hydroxyapatite has been demonstrated
to suppress the progression of hydroxyapatite dissolution in
acidic environment caused by osteoclastic bone resorption
in the body.[5c,6] In addition, the growth of apatite on Ca-
TiO3 is promoted in simulated body fluids.[7] The good sta-
Electrospinning is a highly versatile method for prepar-
ing fibers with dimensions down to the nanometer range.
Electrospun nanofibers offer several advantages such as an
extremely high surface-to-volume ratio, tunable porosity,
and malleability to conform to a wide variety of sizes and
shapes.[11] With smaller pores and higher surface area than
regular fibers, electrospun fibers have been successfully ap-
plied in diverse fields including tissue engineering,[12] bio-
sensors,[13] filtration,[14] wound dressings,[15] drug deliv-
ery,[1a,1b,16] and enzyme immobilization.[17] The nanoscale
fibers are generated by the application of a strong electric
field to the polymer solution. Under a strong electric field,
a jet is formed and moves towards the grounded collector.
On the way to the collector, the solvent evaporates, and so-
lid fibers with diameters ranging from micrometers to na-
nometers precipitate on the collector. The electrospinning
technique has been utilized to synthesize dense and hollow
nanofibers of inorganic ceramics such as silica,[18] bioactive
glass,[3b] TiO2,[19] SnO2,[20] Al2O3,[21] In2O3,[22] and Ca-
TiO3.[23] Electrospinning has been proven to be a highly
successful technique for controlling the synthesis of one-
dimensional nanostructures.
[a] State Key Laboratory of Silicon Materials,
School of Materials Science and Engineering,
Zhejiang University,
Hangzhou 310027, P. R. China
E-mail: xiang.li@zju.edu.cn
hgr@zju.edu.cn
[b] Department of Chemistry & Biochemistry,
Stephenson Life Sciences Research Center,
University of Oklahoma,
CaTiO3 nanofibers doped with rare earth elements have
been synthesized by electrospinning for various optical ap-
plications.[24] However, to the best of our knowledge, there
is no report on electrospun CaTiO3 nanofibers for localized
drug-delivery applications. Therefore, in this work we fabri-
101 Stephenson Parkway, Norman, Oklahoma 73019-5300,
USA
E-mail: cbmao@ou.edu
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201500737.
Eur. J. Inorg. Chem. 2015, 4532–4538
4532
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
FULL PAPER
cated nanoscale CaTiO3 drug carriers with a method based
on the electrospinning technique with subsequent heat
treatment. A surfactant-assisted sol–gel method was uti-
lized to realize the controllable synthesis of CaTiO3 nano-
fibers with use of Pluronic F127 as surfactant and by tuning
the experimental parameters. The drug-release properties of
the nanofibers were tested with ibuprofen (IBU) as a model
drug.
Results and Discussion
Electrospinning Synthesis Process and Phase Structure
A schematic diagram of the electrospinning procedure of
CaTiO3 nanofibers is shown in Figure 1. The setup has
three components: a high-voltage power supply, a metallic
needle, and a grounded collector (Figure 1a). The needle is
connected to a syringe in which the precursor solution is
filled. With use of a syringe pump, the solution is fed
through the needle at a controllable rate. When a high volt-
age is applied, the pendant droplet of the precursor solution
at the tip of the needle becomes highly electrified, and the
Figure 1. (a) Schematic diagram of electrospinning setup. (b–d) The
high-speed camera image of the jet during electrospinning at dif-
ferent voltages. The scale bar is 1 mm.
induced charges get evenly distributed over the surface. As about 9.89% weight loss in the TG curve, was accompanied
a result, under the coulombic force exerted by the external with a weak broad endothermic peak at 74.58 °C due to the
electric field and the electrostatic repulsion between the sur- evaporation of residual solvent. Between 157.2 and
face charges, the droplet is distorted to a hemispherical ob- 329.92 °C, about 69.61% weight loss was observed with two
ject and is elongated to form a conical shape known as the exothermic peaks at 219.01 and 312.66 °C, which are attrib-
Taylor cone.[25]
uted to the decomposition of nitrates and the degradation
In our study, when the applied voltage and flow rate were of polyvinylpyrrolidone (PVP).[27] PVP degradation pro-
set at 9.8–10.6 kV and 0.5 mL/h, respectively, a stable cone- ceeds by two mechanisms involving both intramolecular
shaped electrospinning jetting mode was achieved and and intermolecular transfer reactions.[28] Between 329.92
maintained, as captured by a speed camera (Figure 1c). and 550 °C, there was about 4.31% weight loss with an exo-
Subsequently, the jet that is highly stretched and elongated thermic peak at 463.15 °C, which is the result of oxidation
under the electric field results in the formation of con- of carbon and carbon monoxide released by the decomposi-
tinuous fine fibers owing to the blending instability.[26] tion of tetrabutyltitanate and PVP.[27,29] No further signifi-
When the process parameters were set outside this range, cant weight loss was observed above 600 °C, indicating that
an unstable jetting mode (Figure 1b) or a multijetting mode the pyrolysis process was complete and the perovskite Ca-
(Figure 1d) were obtained, as a result of which non-uniform TiO3 phase was formed.
fibers were formed.
Figure 2b shows X-ray diffraction (XRD) patterns of the
Figure 2a shows the thermogravimetric differential scan- fibers annealed at 700 °C, well-defined diffraction peaks at
ning calorimetry (TG-DSC) curves of the as-spun fibers (110), (111), (112), (210), (103), (022), (220), (204), (224),
during the calcination process by heating known quantities and (110) were detected, all of which were indexed to the
of fibers at a step rate of 10 °C/min in air. An increase from orthorhombic phase of CaTiO3 (JCPDS No. 82–0228). No
ambient temperature (25 °C) to 157.2 °C, which resulted in diffraction peaks from impurities were observed. This sug-
Figure 2. (a) TG-DSC curves of as-spun CaTiO3 nanofibers and (b) XRD patterns of CaTiO3 nanofibers annealed at 700 °C.
Eur. J. Inorg. Chem. 2015, 4532–4538
4533
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
FULL PAPER
gests that the fibers have crystallized in the pure ortho-
rhombic CaTiO3 phase, which is in agreement with TG-
DSC results.
Effect of Precursor Composition on the Fibers
In the preparation of the CaTiO3 precursor sol, acetic
acid retards the hydrolysis of titanium and stabilizes the sol
for electrospinning. In addition, acetic acid can also absorb
the moisture in the air, which decelerates the evaporation of
the solvents and may induce a negative influence on the fine
fiber morphology. Thus, it is of great importance to control
the volume of acetic acid in the precursor solution. The
influence of the ratio of ethanol to acetic acid on the fiber
morphology was investigated experimentally, and sols with
five different volume ratios of ethanol to acetic acid (1.25,
2, 3, 3.5, and 4) were prepared and electrospun, while keep-
ing the other parameters constant. All the above as-spun
CaTiO3 nanofibers were calcined at 700 °C to eliminate
PVP, surfactant, and solvent. As shown in the scanning
electron microscopy (SEM) images (Figure 3), CaTiO3
nanofibers obtained at different ratios presented different
morphologies. When the volume ratio was set at 4, a white
precipitate formed, and the precursor solution became un-
stable. When the ratio was set at 3 and 3.5, the nanofibers
presented a mean diameter of about 106 and 114 nm,
respectively, and when the ratio was less than 3, the hydro-
lysis of titanium butoxide was effectively hindered,[30] and
the precursor was quite stable. However, curved ribbon-like
CaTiO3 was formed when the volume ratio of ethanol to
acetic acid reached 1.25. The morphology of electrospun
one-dimensional nanomaterials is dependent on a number
of processing parameters including the type of polymer,
electrical conductivity, surface tension, applied voltage,
flow rate, nozzle-collector distance, and operational condi-
tions.[31] Under the control of these factors, evaporation of
the solvent and the subsequent collapse of the fiber might
be responsible for the emergence of a ribbon-like struc-
ture.[32] Once the fiber is spun out of the nozzle during elec-
trospinning, the solvent evaporates rapidly from the fiber,
and the as-prepared fiber may completely solidify to dif-
ferent degrees before reaching the collector. This depends
on the physical properties of the solvents. If the fibers are
not completely solidified prior to reaching the collector, rib-
bon-like structures may form.[33]
Figure 3. SEM images of CaTiO3 nanofibers obtained at various
volume ratios of ethanol to acetic acid: (a) 1.25, (b) 2, (c) 3, and
(d) 3.5. CaTiO3 nanofibers in (d) seem to be cut during the strong
sonication procedure while the sample was collected prior to exami-
nation by SEM. The scale bar is 1 μm.
nanofibers when different amounts of Pluronic F127, a
widely used surfactant in drug-delivery systems, were used
were investigated (Figure 4). Owing to the different penetra-
tion depth of electrons in different parts of the fiber body,
the highly porous nature of all fibers was clearly observed.
The microstructure of nanofibers prepared with F127 sur-
factant shows relatively more “loosened” characteristics
(Figure 4b and 4e). This indicates that the F127 surfactant
induces pores with increased dimensions. In addition, the
polycrystalline nature of CaTiO3 nanofibers is confirmed
from the selected area electron diffraction patterns (the in-
sets of Figure 4b and 4e). The HRTEM images, shown in
Figure 4c and 4f, present a large scale of neatly arranged
lattice fringes with no obvious defects. The d-spacing values
are 0.382 and 0.270 nm, corresponding to the (110) and
(112) crystal facets of the orthorhombic CaTiO3 phase,
respectively. Those results indicate that all fibers are of fine
crystallinity, which agrees well with the findings from XRD
studies.
It needs to be pointed out that acetic acid is a hygro-
scopic liquid with a high boiling point and ethanol is vola-
tile at ambient temperature. When the jets are electrospun
out of the nozzle, ethanol evaporates completely, while
some acetic acid remains in the fiber prepared with a low
volume ratio, giving rise to the formation of curved ribbon-
like morphology. Thus, the volume ratio of ethanol to acetic
acid plays an important role in fiber formation and struc-
ture.
The CaTiO3 nanofibers synthesized with a volume ratio
of 3 were further examined by using transmission electron
Figure 4. TEM and HRTEM images of CaTiO3 nanofibers ob-
tained with (a–c) and without (d–f) F127 surfactant. Insets: SAED
microscopy (TEM). The microstructural characteristics of pattern of a single nanofiber.
Eur. J. Inorg. Chem. 2015, 4532–4538
4534
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
FULL PAPER
The formation mechanism of porous CaTiO3 nanofibers
is demonstrated in Figure 5. The precursor solution is com-
posed of a metal salt solution, PVP, and F127 surfactant.
PVP was used to adjust the viscoelastic behavior and make
the sol suitable for further electrospinning. Pluronic F127
is an amphiphilic block copolymer, which has a large solu-
bility difference between its hydrophilic and hydrophobic
segments. Such copolymer molecules self-assemble into mi-
celles, a core-shell architecture, where hydrophobic seg-
ments are segregated from the exterior solution to form an
inner core surrounded by a shell of hydrophilic segments.[34]
The F127 micelles can exist in the as-spun fibers. Under Figure 6. N2 adsorption/desorption isotherm of CaTiO3 nanofi-
bers.
high-temperature sintering, CaTiO3 nanofibers with porous
structure are obtained, because the F127 micelle template
Table 1. The BET surface area, pore volume, and drug-loading ca-
pacity of CaTiO3 nanofibers.
and PVP molecules vanish. Thus, CaTiO3 nanofibers pre-
pared with or without F127 surfactant have different po-
rous microstructures.
Sample
BET surface area Pore volume Drug-loading capacity
(m2/g)
(cm3/g)
(wt.-%)
Without F127
With F127
30.7
18.1
0.119
0.071
43.7
24.5
Drug Loading and Release
Figure 7 shows the FTIR spectra of CaTiO3 nanofibers,
IBU-loaded CaTiO3 nanofibers, and the pure IBU drug.
For the CaTiO3 nanofibers, strong absorption peaks at
about 445 and 556 cm–1 are attributed to the bending mode
of Ti–O.[36] The weak bands assigned to the hydroxyl ab-
sorption (3432 cm–1) and the O–H vibrations of H2O
(1635 cm–1) indicate the presence of hydroxyl groups and
H2O molecules on the surface of CaTiO3 nanofibers, which
is important for the attachment IBU molecules. When Ca-
TiO3 nanofibers were loaded with IBU molecules, typical
characteristic peaks assignable to –COOH vibration at
about 1720 cm–1 and C–Hx bonds at about 2862 and
2960 cm–1 were clearly observed, except for a slight decrease
in intensity compared with that of pure IBU drug. Further-
more, absorption bands, which could be assigned to the
quaternary carbon atom at about 1460 and 1512 cm–1 and
to the tertiary carbon atom at 1329 cm–1 arising from the
introduced IBU molecules, were also observed, confirming
that IBU drug was successfully loaded on the CaTiO3 nano-
fibers.
Figure 5. Illustration of the formation process of porous CaTiO3
nanofibers.
The unique microstructure characteristics of CaTiO3
nanofibers facilitate the potential of this material as a local-
ized drug-delivery system. To further investigate the poros-
ity of CaTiO3 nanofibers, the specific surface area and pore
characteristics of fibers were examined by using N2 adsorp-
tion/desorption measurements. As shown in Figure 6, Ca-
TiO3 nanofibers prepared with or without F127 surfactant
both showed representative IV-type isotherms, which are
characteristics of typical porous materials. The specific sur-
face area and pore volume of the fibers, calculated using
the Brunauer–Emmett–Teller (BET) and Barrett–Joyner–
Halenda (BJH) methods, are summarized in Table 1. The
fibers synthesized with F127 have a BET surface area of
about 18.1 m2/g and a pore volume of about 0.071 cm3/g,
while those synthesized without the surfactant were found
to show a higher BET surface area (ca. 30.7 m2/g) and a
larger pore volume (ca. 0.119 cm3/g). The reason for such a
difference is the formation of F127 micelles, as discussed
above. This result matches those reported previous-
ly.[2a,34a,35]
Figure 7. (a) FTIR spectra of CaTiO3 nanofibers, IBU-loaded Ca-
TiO3 nanofibers, and pure IBU. (b) The molecular structure of
IBU.
The absorbance of IBU in phosphate-buffered saline
(PBS) solution is shown in Figure S1a. Obviously, the maxi-
Eur. J. Inorg. Chem. 2015, 4532–4538
4535
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
FULL PAPER
mum absorbance occurs at a characteristic wavelength of localized tumor therapy, which require sustained release to
222 nm. Therefore, the in vitro examination of IBU release reduce the significant side effects of the drugs.
by UV/Vis spectroscopy was carried out at this wavelength.
The relationship between absorbance at 222 nm and IBU
concentration is demonstrated in Figure S1b. When the
IBU concentration ranges from 0.010 to 0.025 mg/mL, the
absorbance at 222 nm shows good linearity with the IBU
concentration, and the correlation coefficient reaches
99.408%. The IBU concentration in the release medium can
be calculated by the equation:
A222 = 31.402 CIBU + 0.1488
where A222 is the absorbance at 222 nm and CIBU is the
concentration of IBU in the collected sample. Hence, the
drug-loading capacity and cumulative drug release can be
Figure 8. Cumulative drug-release profiles as a function of release
time for IBU-loaded CaTiO3 nanofibers.
calculated by means of the above calibration curve equa-
tion.
In the drug-loading procedure, the IBU molecules can
be adsorbed onto the surface of the highly porous CaTiO3
Conclusions
A range of CaTiO3 nanofibers with controlled micro-
structure were synthesized by a combination of the sol–gel
and electrospinning methods. By tuning the volume ratio of
ethanol to acetic acid, the morphology of CaTiO3 nano-
fibers can be transformed from nanofibers with a circular
cross section to ribbon-like fibers. The formation of the rib-
bon-like structure is ascribed to inadequate solvent evapo-
ration from the precursor fiber before it reaches the collec-
tor. Amphiphilic block copolymer Pluronic F127 was used
to vary the pore structure of CaTiO3 nanofibers through
self-assembly of F127 micelles and subsequent calcination.
Thus the drug-loading capacity and drug-release behavior
of the CaTiO3 nanofibers were manipulated by altering
their microstructure. As a result of their high surface area,
large pore volume, and small pore dimensions, the CaTiO3
nanofibers synthesized without F127 present the highest
drug-loading capacity and most sustained drug-release ki-
netics. The study has suggested that such CaTiO3 nano-
fibers with unique mesoporous microstructure can serve as
a promising localized drug-delivery system for modern bio-
medical applications.
nanofibers. The drug-loading capacities of the IBU-loaded
CaTiO3 nanofibers prepared with and without F127 surfac-
tant were calculated to be about 24.5 and 43.7 wt.-%,
respectively. It is interesting to find that the amount of drug
loaded on the fibers prepared without F127 surfactant is
nearly double that loaded on the fibers prepared with sur-
factant. Moreover, the BET surface area and pore volume
of the fibers prepared without surfactant are also nearly
two times those of the fibers prepared with the surfactant,
which indicates a correlation between the drug-loading ca-
pacity and the BET surface area and pore volume of the
porous materials.
During the drug-release process in PBS solution, ac-
companied by fluid diffusion into the pores of the nano-
fibers, IBU molecules are liberated from the fibers and re-
leased into the fluid by a diffusion-controlled mechanism.
Figure 8 shows the cumulative drug-release profiles as a
function of release time for IBU-loaded CaTiO3 nanofibers.
Rather different release behavior was observed for the two
types of CaTiO3 nanofibers. A typical drug-release phe-
nomenon consists of two stages, including an initial fast-
release stage, dominated by the rapid leaching of free IBU
molecules from the outer surfaces of the fibers, and a rela-
tively slow subsequent release stage, ascribed to drug libera- Experimental Section
tion from the porous structure of the fibers. The CaTiO3
Reagents and Materials: Calcium nitrate tetrahydrate [Ca(NO3)2·
nanofibers synthesized without F127 surfactant present a
dramatically sustained drug-release rate due to their re-
duced pore dimensions and increased BET surface area.
About 28 wt.-% of IBU drug is liberated from the nano-
fibers within the initial 2 h, and about 66 wt.-% of the total
IBU drug is released after 48 h. In contrast, for the CaTiO3
nanofibers with low BET surface area and large pore di-
mensions, the amount of released IBU drug reaches about
48 and 66 wt.-% within the initial 2 and 8 h, respectively.
Therefore, the drug-loading capacity and the drug-release
behavior have been successfully manipulated by the synthe-
sis of CaTiO3 nanofibers with varied microstructure. Our
findings suggest another promising localized drug-delivery
4H2O, 99%], titanium butoxide [Ti(OC4H9)4, Ͼ98.0%], polyvinyl-
pyrrolidone (PVP, MW = 1,300,000, Aladdin), Pluronic F127
(EO106PO70EO106, MW = 12600, Sigma–Aldrich), Ibuprofen (IBU,
99%, Nanjing Chemical Regent Co., Ltd.), acetic acid (C2H4O2,
A.R.), ethanol (C2H6O, A.R.), N,N-dimethylformamide (C3H7NO,
A.R.), and phosphate-buffered saline (PBS, pH = 7.4, Sinopharm
Chemical Reagent Co., Ltd) were used as received without further
purification.
Fabrication of CaTiO3 Nanofibers
Briefly, Ti(OC4H9)4 (ca. 0.82 g) and Ca(NO3)2·4H2O (ca. 0.56 g)
were dissolved in a mixed solution (9 mL) containing acetic acid
and ethanol (volume ratio of ethanol to acetic acid 1.25, 2, 3, 3.5,
and 4) with magnetic stirring. Then surfactant (Pluronic F127, 1.26
system for a variety of pharmaceutical applications such as wt.-%) and polyvinylpyrrolidone (PVP, 3.25 wt.-%) were added
Eur. J. Inorg. Chem. 2015, 4532–4538
4536
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
FULL PAPER
[2] a) Z. Chen, X. Li, H. He, Z. Ren, Y. Liu, J. Wang, Z. Li, G.
Shen, G. Han, Colloids Surf. B 2012, 95, 274–278; b) Z. Xu, S.
Liu, Y. Kang, M. Wang, Nanoscale 2015, 7, 5859–5868.
[3] a) S. Huang, X. Kang, Z. Cheng, P. Ma, Y. Jia, J. Lin, J. Colloid
Interface Sci. 2012, 387, 285–291; b) Y. Hong, X. Chen, X.
Jing, H. Fan, Z. Gu, X. Zhang, Adv. Funct. Mater. 2010, 20,
1503–1510; c) Y. Li, B. Li, G. Xu, Z. Ahmad, Z. Ren, Y. Dong,
X. Li, W. Weng, G. Han, Colloids Surf. B 2014, 122, 785–791.
[4] Z. Hou, P. Yang, H. Lian, L. Wang, C. Zhang, C. Li, R. Chai,
Z. Cheng, J. Lin, Chem. Eur. J. 2009, 15, 6973–6982.
[5] a) P. Huang, K. W. Xu, Y. Han, Mater. Lett. 2005, 59, 185–
189; b) H. Tang, F. Wang, Mater. Lett. 2013, 93, 427–430; c)
J. P. Wiff, V. M. Fuenzalida, J. L. Arias, M. S. Fernandez, Ma-
ter. Lett. 2007, 61, 2739–2743.
with N,N-dimethylformamide solution and stirred for another 6 h
to form spinnable precursor sols.
The electrospinning sol was fed into the conducting nozzle (2 mm
inner diameter) by using an infusion pump (KDS-100, KD Scien-
tific, USA) at a constant flow rate of 0.5 mL/h. The distance and
voltage applied between the needle tip and the collector were set at
15 cm and 10 kV (PS/FC30P04.0–22, Glassman High voltage Inc.,
USA), respectively. As-spun fibers were dried overnight at 80 °C
and calcined in air at 700 °C for 2 h, with a heating rate of 2 °C/
min.
Characterization: The thermal behavior, crystal structure, mor-
phology, and microstructure were investigated by using TG-DSC
(DSCQ1000, AT, USA, air atmosphere), XRD (XЈPertPRO MPD,
Netherlands, using Cu-Kα radiation, λ = 0.1540598 nm), SEM (FE
SEM, Hitachi SU-70, Japan), and TEM (Philips TecnaiF20 S-
TWIN, Netherlands), respectively. The specific surface area and
pore size distribution were determined by N2 adsorption/desorp-
tion analysis at liquid nitrogen temperature (77 K) by using a
Coulter OMNISORP-100 apparatus. The FTIR spectra were re-
corded with a Perkin–Elmer 580B infrared spectrophotometer on
KBr pellets (Tensor 27, Bruker, Germany). UV/Vis absorption val-
ues were measured with a TU-1810 spectrophotometer.
[6] a) G. M. S. Kaciulis, L. Pandolfi, M. Cavalli, G. Gnappi, A.
Montenero, Appl. Surf. Sci. 1999, 151, 1–5; b) S. Holliday, A.
Stanishevsky, Surf. Coat. Technol. 2004, 188, 741–744.
[7]
a) K. Asami, K. Saito, N. Ohtsu, S. Nagata, T. Hanawa, Surf.
Interface Anal. 2003, 35, 483–488; b) T. J. Webster, C. Ergun,
R. H. Doremus, W. A. Lanford, J. Biomed. Mater. Res., Part A
2003, 67, 975–980.
[8]
X. F. Yang, J. X. Fu, C. J. Jin, J. A. Chen, C. L. Liang, M. M.
Wu, W. Z. Zhou, J. Am. Chem. Soc. 2010, 132, 14279–14287.
O. Ruzimuradov, G. Hasegawa, K. Kanamori, K. Nakanishi,
J. Am. Ceram. Soc. 2011, 94, 3335–3339.
[9]
[10]
D. B. Yu, J. H. Zhang, F. Wang, M. H. Zhao, K. Du, S. W.
Shu, J. W. Zou, Y. Wang, Cryst. Growth Des. 2013, 13, 3138–
3143.
Drug Loading and Release
IBU-release measurements were carried out by UV/Vis absorption
spectroscopy. The absorbance values were measured at a character-
istic wavelength of 222 nm, at which the IBU-release medium shows
the maximum absorbance. A calibration curve was drawn by plot-
ting absorbance vs. IBU concentration.
[11]
[12]
N. Bhardwaj, S. C. Kundu, Biotechnol. Adv. 2010, 28, 325–347.
a) E. M. Jeffries, R. A. Allen, J. Gao, M. Pesce, Y. D. Wang,
Acta Biomaterials 2015, 18, 30–39; b) C. H. Ru, F. L. Wang,
M. Pang, L. N. Sun, R. H. Chen, Y. Sun, ACS Appl. Mater.
Interfaces 2015, 7, 10872–10877; c) J. Thunberg, T. Kalogero-
poulos, V. Kuzmenko, D. Hagg, S. Johannesson, G. Westman,
P. Gatenholm, Cellulose 2015, 22, 1459–1467.
In the drug-loading procedure, CaTiO3 nanofibers (300 mg) were
suspended in a hexane solution of IBU (40 mg/mL, 50 mL) at am-
bient temperature and stirred for 24 h to induce the diffusion of
the drug into the pores. Then, the nanofibers were collected by
centrifugation and washed with hexane to remove the IBU ad-
sorbed on the outer surface. The filtrate (1 mL) was collected and
diluted for the measurement of drug-loading capacity by UV/Vis
spectroscopy at a wavelength of 222 nm.
[13]
a) N. Promphet, P. Rattanarat, R. Rangkupan, O. Chailapakul,
N. Rodthongkum, Sensor Actuat. B-Chem. 2015, 207, 526–534;
b) P. P. Zhang, X. N. Zhao, Y. C. Ji, Z. F. Ouyang, X. Wen,
J. F. Li, Z. Q. Su, G. Wei, J. Mater. Chem. B 2015, 3, 2487–
2496.
[14]
[15]
a) Z. Wang, C. C. Zhao, Z. J. Pan, J. Colloid Interface Sci.
2015, 441, 121–129; b) X. Q. Li, N. Wang, G. Fan, J. Y. Yu, J.
Gao, G. Sun, B. Ding, J. Colloid Interface Sci. 2015, 439, 12–
20.
a) A. Lowe, J. Bills, R. Verma, L. Lavery, K. Davis, K. J.
Balkus, Acta BioMater. 2015, 13, 121–130; b) R. Zhao, X. Li,
B. L. Sun, Y. Tong, Z. Q. Jiang, C. Wang, Rsc Adv. 2015, 5,
16940–16949.
In vitro drug release was investigated after IBU-loaded CaTiO3
nanofibers were dried overnight at 60 °C. IBU-loaded CaTiO3
nanofibers (200 mg) were immersed in the release medium PBS
with gentle stirring at 37 °C. At each selected time interval, an ali-
quot (1 mL) was collected and immediately replaced with an equal
volume of fresh PBS. The samples collected were diluted and ana-
lyzed by UV/Vis spectroscopy at a wavelength of 222 nm.
[16]
[17]
Z. Hou, C. Li, P. Ma, G. Li, Z. Cheng, C. Peng, D. Yang, P.
Yang, J. Lin, Adv. Funct. Mater. 2011, 21, 2356–2365.
a) R. Xu, Y. F. Si, F. T. Li, B. R. Zhang, Environ. Sci. Pollut.
Res. Int. 2015, 22, 3838–3846; b) C. Tang, C. D. Saquing, S. W.
Morton, B. N. Glatz, R. M. Kelly, S. A. Khan, ACS Appl. Ma-
ter. Interfaces 2014, 6, 11899–11906.
Acknowledgments
[18]
W. Wang, J. Zhou, S. Zhang, J. Song, H. Duan, M. Zhou, C.
Gong, Z. Bao, B. Lu, X. Li, W. Lan, E. Xie, J. Mater. Chem.
2010, 20, 9068.
This work was financially supported by the National Nature Sci-
ence Foundation of China (No. 51232006), the “Qianjiang” Talent
Program of Zhejiang Province (2013R10037), and the Nature Sci-
ence Foundation of Zhejiang Province (LY15E020005). C. M.
would like to thank for the financial support from National Insti-
tutes of Health (EB015190) and National Science Foundation
(CMMI-1234957).
[19] a) K. Tang, Y. Yu, X. Mu, P. A. van Aken, J. Maier, Electro-
chem. Commun. 2013, 28, 54–57; b) D. Li, Y. N. Xia, Nano
Lett. 2003, 3, 555–560.
[20]
[21]
[22]
[23]
[24]
W. Q. Li, S. Y. Ma, J. Luo, Y. Z. Mao, L. Cheng, D. J. Geng-
zang, X. L. Xu, S. H. Yan, Mater. Lett. 2014, 132, 338–341.
P. P. Zhang, D. R. Chen, X. L. Jiao, Eur. J. Inorg. Chem. 2012,
4167–4173.
Z. P. Li, Y. J. Fan, J. H. Zhan, Eur. J. Inorg. Chem. 2010, 3348–
3353.
Q. Zhang, Y. Li, Z. Ren, Z. Ahmad, X. Li, G. Han, Mater.
Lett. 2015, 152, 82–85.
a) C. Peng, Z. Hou, C. Zhang, G. Li, H. Lian, Z. Cheng, J.
Lin, Opt. Express 2010, 18, 7543–7553; b) G. P. Dong, X. D.
[1] a) Z. Y. Hou, X. J. Li, C. X. Li, Y. L. Dai, P. A. Ma, X. Zhang,
X. J. Kang, Z. Y. Cheng, J. Lin, Langmuir 2013, 29, 9473–9482;
b) Y. Hong, X. Chen, X. Jing, H. Fan, B. Guo, Z. Gu, X.
Zhang, Adv. Mater. 2010, 22, 754–758; c) M. Vallet-Regi, A.
Ramila, R. P. del Real, J. Perez-Pariente, Chem. Mater. 2001,
13, 308–311.
Eur. J. Inorg. Chem. 2015, 4532–4538
4537
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.eurjic.org
FULL PAPER
Xiao, L. L. Zhang, Z. J. Ma, X. Bao, M. Y. Peng, Q. Y. Zhang,
J. R. Qiu, J. Mater. Chem. 2011, 21, 2194–2203.
Uhrich, S. M. Cannizzaro, R. S. Langer, K. M. Shakesheff,
Chem. Rev. 1999, 99, 3181–3198; d) K. Kataoka, A. Harada,
Y. Nagasaki, Adv. Drug Delivery Rev. 2001, 47, 113–131.
[25] a) A. Frenot, I. S. Chronakis, Curr. Opin. Colloid Interface Sci.
2003, 8, 64–75; b) D. H. Reneker, I. Chun, Nanotechnology
1996, 7, 216–223; c) Y. M. Shin, M. M. Hohman, M. P.
Brenner, G. C. Rutledge, Appl. Phys. Lett. 2001, 78, 1149–1151;
d) D. H. Reneker, A. L. Yarin, H. Fong, S. Koombhongse, J.
Appl. Phys. 2000, 87, 4531–4547.
[26] a) A. L. Yarin, S. Koombhongse, D. H. Reneker, J. Appl. Phys.
2001, 90, 4836–4846; b) Y. M. Shin, M. M. Hohman, M. P.
Brenner, G. C. Rutledge, Polymer 2001, 42, 9955–9967.
[27] L. L. Wang, X. M. Liu, Z. Y. Hou, C. X. Li, P. P. Yang, Z. Y.
Cheng, H. Z. Lian, J. Lin, J. Phys. Chem. C 2008, 112, 18882–
18888.
[33]
[34]
T. J. Sill, H. A. von Recum, Biomaterials 2008, 29, 1989–2006.
a) J. Saha, G. De, Chem. Commun. 2013, 49, 6322–6324; b) W.
Zhao, Y. L. Su, C. Li, Q. Shi, X. Ning, Z. Y. Jiang, J. Membr.
Sci. 2008, 318, 405–412.
[35] a) D. Grosso, G. J. d. A. A. Soler-Illia, E. L. Crepaldi, F. Cag-
nol, C. Sinturel, A. Bourgeois, A. Brunet-Bruneau, H. Amen-
itsch, P. A. Albouy, C. m. Sanchez, Chem. Mater. 2003, 15,
4562–4570; b) P. D. Yang, D. Y. Zhao, B. F. Chmelka, G. D.
Stucky, Chem. Mater. 1998, 10, 2033–2036.
[36] a) S. Maensiri, W. Nuansing, J. Klinkaewnarong, P. Laokul, J.
Khemprasit, J. Colloid Interface Sci. 2006, 297, 578–583; b)
H. K. Yang, J. W. Chung, G. S. R. Raju, B. K. Moon, B. C.
Choi, J. H. Jeong, J. H. Kim, Appl. Surf. Sci. 2009, 255, 5062–
5066; c) M. Shivaram, H. Nagabhushana, S. C. Sharma, S. C.
Prashantha, B. Daruka Prasad, N. Dhananjaya, R.
Hari Krishna, B. M. Nagabhushana, C. Shivakumara, R. P.
Chakradhar, Spectrochim. Acta Part A 2014, 128, 891–901.
Received: July 5, 2015
[28] S. J. A. M. A. Dish, Polym. Degrad. Stab. 1998, 60, 253–256.
[29] C. Peng, Z. Hou, C. Zhang, G. Li, H. Lian, Z. Cheng, J. Lin,
Opt. Express 2010, 18, 7543–7553.
[30] Y. Fu, Z. Jin, Y. Ni, H. Du, T. Wang, Thin Solid Films 2009,
517, 5634–5640.
[31] A. Greiner, J. H. Wendorff, Angew. Chem. Int. Ed. 2007, 46,
5670–5703; Angew. Chem. 2007, 119, 5770.
[32] a) D. Li, Y. N. Xia, Adv. Mater. 2004, 16, 1151–1170; b) X.
Guo, F. C. Szoka, Acc. Chem. Res. 2003, 36, 335–341; c) K. E.
Published Online: August 18, 2015
Eur. J. Inorg. Chem. 2015, 4532–4538
4538
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim