Beruflich Dokumente
Kultur Dokumente
a r t i c l e i n f o a b s t r a c t
Article history: Novel physically cross-linked cryogels containing polyvinyl alcohol (PVA) and various amounts of microcrys-
Received 12 April 2012 talline cellulose were obtained by freezing/thawing technique. The main goal of this study was to improve
Received in revised form 11 June 2012 the properties and the performances of the pure PVA cryogels. The morphological aspects of the cryogels
Accepted 20 July 2012
were studied by scanning electron microscopy (SEM). The Fourier transform infrared spectroscopy (FT-IR)
Available online 27 July 2012
was used to reveal the presence of the interactions between the two polymers. Changes in crystallinity of
Keywords:
the samples were confirmed by X-ray diffraction (XRD) and by FT-IR spectroscopy. The modification of the
Polyvinyl alcohol thermal behavior induced by cellulose was studied by thermogravimetry. Rheological analysis revealed
Cellulose higher values of storage modulus (G′) for the cryogels containing higher amounts of cellulose. The degree
Cryogels and rate of swelling were controlled by the presence of the natural polymer in the network. The potential
Freezing-thawing application as bioactive compound carriers was tested, using vanillin as an active agent.
Bioactive compound © 2012 Elsevier B.V. All rights reserved.
Release
1. Introduction crosslinked hydrogels, cryogels show higher elasticity and have in-
creased strength due to the crystalline regions which are capable of
Hydrogels are hydrophilic three-dimensional networks of poly- better distributing a given mechanical load or stress [11,12].
mer chains which are capable of absorbing large amounts of water PVA cryogels have been studied as controlled release carriers, as
or biological fluids [1]. Due to their properties, hydrogels have nu- barrier film for food packaging, as material for the preparation of
merous applications, including contact lenses, membranes for biosen- membranes used in chemical separation, as biomaterial in tissue en-
sors, carriers for drug/aroma, in tissue engineering as scaffolds for gineering, as wound dressing materials, food packaging etc. [13–16].
regenerating tissues and organs, as materials for artificial skin, as Wound dressings are used to promote the wound healing and to
cell carriers etc. [2–7]. Cast into films and dried, hydrogels are now create appropriate conditions for this process, while protecting the
being used as biodegradable packaging materials for food, cosmetic wound from infections. It is widely accepted that a moist environ-
and pharmaceutical products [8]. Cryogels refer to hydrogels formed ment is desirable to enhance the wound healing so, some hydrogels
at subzero temperature which provide special properties for different are being used with success as wound dressings, because they assure
bioengineering and biotechnological applications [9]. an appropriate level of moisture at the interface between the dressing
Polyvinyl alcohol (PVA) is a water-soluble, non-toxic, biodegrad- and the wound, have the capacity to absorb exudates, prevent the
able, biocompatible synthetic polymer with excellent film forming wound desiccation, are non-adhesive, have a cooling effect giving a
properties [10]. Due to its hydroxyl groups present in each repeating relief feeling to the patient, and in the same time they can deliver
unit, PVA exhibits a strong hydrophilic and hydrogen bonding charac- an incorporated drug to the wound [17–19].
ter; thus it is able to form crosslinked hydrogels. Physical hydrogels The use of natural polymers as components of polymeric materials
(cryogels) can be obtained by exposing PVA aqueous solutions to re- is of great interest, due to the diversity of their properties, but also
peated cycles of freezing and thawing, which results in the formation from economic and ecological reasons. PVA exhibiting high polarity
of crystallites. The main advantage of this technique is that no addi- and water solubility is a good candidate for blends with natural poly-
tional chemical crosslinker is being used. Comparing to chemically mers [20]. Cryogels based on PVA/polysaccharides are suitable as
wound dressing materials because these hydrogels are flexible, me-
chanically strong, biocompatible, can be easily replaced, can assure
a moist wound environment and a barrier against microorganisms
[21–23].
⁎ Corresponding author at: Romanian Academy, “P. Poni” Institute of Macromolecu-
lar Chemistry, 41A Grigore Ghica Voda Alley, 700487, Iasi, Romania. Tel.: +40 0232
Cellulose is the most abundant renewable resource on Earth. Sim-
217454; fax: +40 0232 211299. ilar to PVA hydrogels, cellulose based hydrogels are also hydrophilic,
E-mail address: cvasile@icmpp.ro (C. Vasile). biodegradable, biocompatible, non-toxic [24]. In the human and
0928-4931/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.msec.2012.07.033
O.M. Păduraru et al. / Materials Science and Engineering C 32 (2012) 2508–2515 2509
this polysaccharide is not degradable in the body and is not digestible Sample Cryogels composition (wt%)
due to the fact that human and animal cells do not synthesize cellu-
PVA Cellulose
lases, the enzymes capable of degrading cellulose [25]. All these prop-
PVA 100 0
erties made the cellulose hydrogels suitable for various applications,
90/10 90 10
especially in the biomedical field [26–28]. 70/30 70 30
Scientific literature presented different types of celluloses incor- 50/50 50 50
porated into PVA films and hydrogels, such as bacterial cellulose
[29], cellulose whiskers [30], cellulose nanofibres [31,32], cellulose
nanocrystals [33] and cellulose fibrous powder [34]. Various methods room temperature (+ 25 °C) for another 12 hours. The freezing/
of crosslinking, as well as different methods of cellulose dissolution thawing process was repeated three times.
have been used in these kinds of studies. For example, Millon et al. The blank PVA cryogel was prepared pouring a certain amount of
[29] used freezing/thawing method for obtaining PVA/bacterial cellu- PVA solution in a Petri dish and then exposed to three freezing/
lose cryogels, while Abitbol et al. [33] used the same crosslinking thawing cycles (12 hours freezing/12 hours thawing).
method in order to obtain PVA hydrogels reinforced with cellulose The PVA and the PVA/cellulose cryogels were washed with
nanocrystals from softwood Kraft pulp. Chang et al. [34] prepared distilled water for 3 days and were dried by lyophilization for
hydrogels using fibrous cellulose dissolved in NaOH/urea aqueous so- 24 hours, using a LABCONCO 117 freezing-dryer. Polymeric films
lution and epichlorohydrin as a crosslinking agent. were obtained after lyophilization.
The novelty of this study refers to the obtaining of PVA cryogels Due to the fact that cellulose cryogel could not be obtained by this
containing microcrystalline cellulose by freezing-thawing method by technique, the cellulosic powder was treated in the same conditions
using a special dissolution method for cellulose in a water/NaOH mix- as described above and used as blank sample.
ture, at low temperatures [35]. In our study we also tested the obtained
cryogels as carriers for the delivery of an antimicrobial and antioxidant 2.3. Investigation methods
agent such as vanillin (4-hydroxy-3-methoxybenzaldehyde). Vanillin,
one of the most widely used flavoring agent, is produced naturally in 2.3.1. Scanning electron microscopy (SEM)
the specialized cells from the pods of the Vanilla sp. and synthetically Scanning electron micrographs were taken on liquid nitrogen frac-
from eugenol, guaiacol or lignin [36]. It is being used as a flavoring tured samples, with a Quanta 200 instrument. The fractured surface
and antioxidant agent in food industry, but also in cosmetics and phar- was coated with a gold layer. Magnification is given on the images.
maceutical formulations [37,38]. It has been reported that vanillin ex-
hibits multifunctional effects such as antimutagenic, antiangiogenetic, 2.3.2. X‐ray diffraction measurements (XRD)
anti-colitis, anti-sickling, and analgesic effects [39]. The antimicrobial The measurements were carried out by means of a Bruker AXS D8
properties of vanillin and its activity have been previously demonstrat- Advance X-ray diffractometer with a Cu Kα radiation source. The data
ed against some bacteria (Escherichia coli, Pseudomonas aeruginosa, Lac- were collected in the 2θ = 2 ÷ 40° region. The crystallinity index (CrI)
tobacillus plantarum, Listeria innocua), but also against some yeast and was calculated by the area method, dividing the area of the crystalline
mold strains (Candida albicans, Penicillum expansum, Saccharomyces peak by the total area under diffractogram [42].
cerevisiae) [40,41].
It was expected that the incorporation of microcrystalline cellu- 2.3.3. Fourier transform infrared spectroscopy (FT‐IR)
lose into PVA cryogels lead to an improvement of the properties and The FT-IR analysis was performed on a Vertex-70 (Bruker) appara-
an enhancement of the performances. These cryogels were character- tus, using KBr tablets containing a constant mass of 5 mg sample/
ized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffrac- 500 mg KBr. The spectra were recorded in the 4500–600 cm −1,
tion (XRD), thermal degradation, rheological measurements and “in with 16 scans and a resolution of 4 cm −1. Three recordings were
vitro” tested as drug carriers. Also the kinetics of swelling in phos- done for each system and the average values were used for data inter-
phate buffer solution (PBS) pH 7.4 at 37 °C and of drug release was pretation. The energy of the hydrogen bonds (EH) was calculated
studied. using Eq. (1) [42].
2.1. Materials where k is a constant equal to 1.68 × 10 −2 kcal −1, υ0 is the standard
frequency corresponding to free ―OH groups (3650 cm −1), υ is the
PVA with an average molecular weight of 146 000–186 000 and a frequency of the bonded ―OH groups (cm −1). The enthalpy of the
hydrolysis degree of 99% was purchased from Aldrich. Microcrystal- hydrogen-bond formation (ΔH) was evaluated using Eq. (2) [43]:
line cellulose Avicell PH-101 was purchased from Fluka.
ΔH ðJ=gÞ ¼ 0:016ΔυOH þ 0:63 ð2Þ
2.2. PVA/cellulose cryogels preparation
where ΔυOH is the ―OH wavenumber shift (cm −1). The hydrogen-
bonding distance (R, A°) was obtained using Sederholm Eq. (3) [44].
A PVA solution of 8 wt% concentration was prepared by dissolving
a certain amount of PVA into double distilled water, at 90 °C under
−1 3
stirring for 8 hours. A clear solution was obtained. Δυ cm ¼ 4:43 10 ð2:84−RÞ ð3Þ
Different amounts of microcrystalline cellulose were dispersed in
11/1 water/NaOH (w/w) mixture, stirred for 5 min and then frozen where Δυ = υ0 − υ (υ0 is the ―OH monomeric stretching frequen-
at low temperature (− 30 °C). After defrosting, the obtained solutions cy = 3600 cm −1; υ is the ―OH stretching frequency of the sample).
were stirred in order to obtain clear, transparent solutions [35].
Cellulose and PVA solutions were mixed in different ratios 2.3.4. Thermogravimetry
(Table 1) and stirred for 5 min. The obtained mixtures were poured The thermogravimetric analysis was performed on a Jupiter STA
into Petri dishes and frozen at − 20 °C for 12 hours, then thawed at 449 F1—Netzsch instrument. Samples of 7 mg were heated up to
2510 O.M. Păduraru et al. / Materials Science and Engineering C 32 (2012) 2508–2515
600 °C, with a heating rate of 10 °C/min, in open Al2O3 crucible, under In order to elucidate the kinetics of vanillin release from the
50 ml/min nitrogen flow. studied cryogels, the data were analyzed using the equation proposed
by Korsmeyer and Peppas—Eq. (6). This equation was applied only to
2.3.5. Rheological measurements the first 60% of the total amount of vanillin released.
Rheological measurements were performed with an Anton Paar
nr
MCR301 rheometer, using a measurement system with a plate— Mt =M∞ ¼ kr t ð6Þ
plate geometry of 25 mm diameter and 0.8 mm gap. The samples
were placed between the plates for 5 min to eliminate residual where Mt/M∞ is the fractional release of the active agent (Mt and M∞
shear history and then the experiments were carried out immediate- represents the amounts of active agent released at time t and at equi-
ly. The linear viscoelastic range was determined performing an ampli- librium, respectively), kr is a constant characteristic of the polymer–
tude sweep test at 23 °C, a shear strain of 0.1% being kept during the active agent interaction and nr is the diffusion exponent representing
further rheological tests. The measuring device was equipped with a the release mechanism.
temperature unit that gave good temperature control (±0.05 °C). In For a value of nr = 0.5 the mechanism of the active agent release is
order to evaluate the rheological behavior with increasing tempera- controlled by Fickian diffusion, while a value of nr = 1 indicates that
ture, the cryogels were heated from 20 to 80 °C with a heating rate the release rate is independent of time and controlled by swelling
of 2 °C/min (temperature sweep tests). In the same time an oscillat- mechanism. Values of nr between 0.5 and 1 were regarded as an indi-
ing stress was exerted to the samples with a constant frequency of cator for the superposition of both phenomena. This type of release
1 Hz. mechanism was named anomalous (non-Fickian) transport. [46]
PVA 90/10
70/30 50/50
Fig. 1. SEM images of the cross-section of PVA and PVA/cellulose cryogels (magnification 2000×).
observations are a proof of cryogel formation between those two 3436 cm −1 corresponds to the OH stretching vibration, including
polymers and their mutual influence. the groups which are involved in intramolecular and intermolecular
The crystallinity index (CrI) for PVA was determined as 57%, while hydrogen bonds. This band becomes broader with the addition of cel-
the value for cellulose was found to be 66%. The values obtained for lulose into cryogels, due to the presence of an increased amount of
the PVA/cellulose cryogels were intermediate between the values of OH groups in the samples. The absorption band from 2925 cm −1,
the blank samples. Thus, the sample containing 30 wt% cellulose has which is assigned to the C–H stretching vibration from alkyl groups,
60% crystallinity, while for the sample containing 50 wt% cellulose is shifted to lower wavenumber and its intensity increases with the
the CrI increased to 63%. addition of cellulose. A strong band observed at 1631 cm −1 corre-
sponds to the absorbed water, while the band from 1384 cm −1 has
3.3. FT‐IR measurements been assigned to the vibration of the CH2 groups.
The FT-IR spectra clearly indicate the presence of cellulose into
In Fig. 3 the FT‐IR spectra of blank samples and of the PVA/ these cryogels. The band from 1431 cm −1, assigned to a symmetric
cellulose cryogels are shown. The absorption band which appears at CH2 bending vibration is increasing in intensity with the increase of
140 1,2
PVA
1,0
120 90/10
0,8
70/30
0,6
100
50/50
0,4
Intensity, a.u.
80 0,2 Cellulose
%T
0,0
60 Cellulose
-0,2
40 -0,4
50/50
-0,6
70/30
20 -0,8
PVA
-1,0
0
5 10 15 20 25 30 35 40 4500 4000 3500 3000 2500 2000 1500 1000 500
2θ, degree Wavenumber (cm-1)
Fig. 2. X-ray diffractograms of the PVA, cellulose and their cryogels. Fig. 3. FT‐IR absorption band spectra of PVA, cellulose and PVA/cellulose cryogels.
2512 O.M. Păduraru et al. / Materials Science and Engineering C 32 (2012) 2508–2515
Fig. 4. The TG (a) and DTG (b) curves of PVA, cellulose and PVA/cellulose cryogels.
O.M. Păduraru et al. / Materials Science and Engineering C 32 (2012) 2508–2515 2513
550
500
105
10 5 450
Swelling degree %
400
104 350
G' (Pa)
G'' (Pa)
10 4 300
250
103
200
10 3 150
PVA
102 PVA 100 90/10
90/10
50 70/30
70/30
50/50 10 2 50/50
1 0
10
20 30 40 50 60 70 80 0 100 200 300 400 1380 1400 1420 1440
Temperature ( 0C) Time (min)
Fig. 5. Temperature dependence of the storage modulus (filled symbols) and the loss Fig. 6. Swelling degree of the PVA/cellulose cryogels in phosphate buffer solution (pH
modulus (empty symbols) for the studied cryogels. 7.4) at 37 °C.
2514 O.M. Păduraru et al. / Materials Science and Engineering C 32 (2012) 2508–2515
600
450
30
ESD (%)
400
350 20
300
10
PVA
250 90/10
70/30
200 0
50/50
0 10 20 30 40 50 0 100 200 300 400 1360 1380 1400 1420 1440 1460
% Cellulose Time (min)
Fig. 7. Variation of the ESD with the cellulose content of the cryogels. Fig. 8. Vanillin release profiles from PVA/cellulose cryogels, in phosphate buffer solution
(pH 7.4) at 37 °C.
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[37] D.J. Fitzgerald, M. Stratford, M.J. Gasson, A. Narbad, J. Agric. Food Chem. 53 (2005)
This research was financially supported by the grant of the 1769–1775.
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Romanian National Authority for Scientific Research, CNCS—UEFISCDI, S65–S71.
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