Synthesis and application of photo-active carboxymethyl cellulose derivatives

Article abstract of DOI:10.1016/j.reactfunctpolym.2016.03.013

In this work, the polysaccharide carboxymethyl cellulose (CMC) was first activated via periodate oxidation then modified by insertion of photo-active cinnamic acid hydrazide moieties to finally produce the photo-crosslinkable CMC-CM with various extents of functionalizations. The chemical structures of the manufactured polymeric materials were entirely investigated utilizing FTIR, ¹H, ¹³C NMR, and UV-vis spectra. Upon irradiation in UV light, the progress and kinetics of the cross-linking were detected using UV-vis spectra. Moreover, the crystallinity changes before and after chemical modification and subsequent UV irradiation were examined by XRD spectra. Also, the obtained hydrogels with various cross-linking densities were freeze dried to visualize the morphological changes using SEM. In addition, the rheological experiments indicated the improvement of the hydrogel mechanical properties by increasing both UV irradiation time and degree of cinnamate functionalization. The obtained hydrogel exhibited good swelling, gelation and biodegradation properties, which indicate a promising potential in different biomedical applications.

Full text of DOI:10.1016/j.reactfunctpolym.2016.03.013

Synthesis and application of photo-active carboxymethyl cellulose derivatives
M. Monier, D.A. Abdel-Latif, H.F. Ji
PII:
S1381-5148(16)30045-1
DOI:
Reference:
doi: 10.1016/j.reactfunctpolym.2016.03.013
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22 December 2015
11 March 2016
12 March 2016
Please cite this article as: M. Monier, D.A. Abdel-Latif, H.F. Ji, Synthesis
and application of photo-active carboxymethyl cellulose derivatives, (2016), doi:
10.1016/j.reactfunctpolym.2016.03.013
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Synthesis and application of photo-activecarboxymethyl cellulose
derivatives
M. Monier*a,b, D.A. Abdel-Latifb, H.F. Jic
aChemistry Department, Deanery of Academic Services, Taibah University, Yanbu Branch, Yanbu El-Bahr, KSA
bChemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt
cDepartment of Chemistry, Drexel University, Philadelphia, PA. USA
Abstract
In this work, the polysaccharide carboxymethyl cellulose (CMC) was first
activated via periodate oxidation then modified by insertion of the photo-active
cinnamic acid hydrazide moieties to finally produce the photo-crosslinkable CMC-
CM with various extents of functionalizations. The chemical structures of the
manufactured polymeric materials were entirely investigated utilizing FTIR, 1H,
13C NMR, UV-vis spectra. Upon irradiation in the UV light, the progress and
kinetics of the cross-linking were detected using UV-vis spectra. Moreover, the
crystallinity changes before and after chemical modification and subsequent UV
irradiation were examined by XRD spectra. Also, the obtained hydrogels with
various cross-linking densities were freeze dried to visualize the morphological
changes using SEM. In addition, the rheological experiments indicated the
improvement of the hydrogel mechanical properties by increasing both UV
irradiation time and degree of cinnamte functionalization. The obtained hydrogel
exhibited a good swelling, gelation and biodegradation properties, which indicate a
promising potential in different biomedical applications.
______________________________________________________________
Keywords:
Carboxymethyl cellulose
Cinnamate
Photo-crosslinking
Cycloaddition
_____________________________________________________________________________
* Corresponding author. Chemistry Department, Deanery of Academic Services,
Taibah University, Yanbu Branch, Yanbu El-Bahr, KSA.
Tel.: ‏00966532492041.
E-mail address: monierchem@yahoo.com (M.Monier).
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1. Introduction
Carboxymethyl cellulose (CMC) is regarded as one of the most commonly
used polysaccharide derivatives. As a result of its water solubility, high
availability, biocompatibility in addition to the non-toxicity, CMC had been widely
employed in various industrial applications such as pharmaceutics, cosmetics and
textiles [1-3]. Moreover, the biodegradability of CMC enhanced the utility in
various biotechnological applications such as drug delivery systems, enzyme
immobilization and tissue engineering [4-7]. In most of these biomedical and
pharmaceutical applications, CMC had to be cross-linked to form a three
dimensional polymeric hydrophilic network, which is able to absorb a large
amounts of water and swells until reaching equilibrium between the
thermodynamic swelling forces and cross-linking elastic retractive force. At this
equilibrium point, the obtained polymer-water state called hydrogel [8-10].
Many types of cross-linking agents had been utilized for either ionic or
covalent cross-linking of CMC such as Al3+ ions [11, 12]1,4-Butanediol diglycidyl
ether [13], polyethylene glycol diglycidyl ether (PEGDE) [14], dicarboxylic acids
[15] in addition to epichlorohydrin (ECH), which is a common CMC cross-linking
agent due to the high tendency to form ether linkage with the –OH groups [16-18].
All the aforementioned cross-linking agents were efficiently employed in
manufacturing CMC based hydrogels for various biomedical and environmental
applications. However, formation of carcinogenic and even toxic byproducts
during the biodegradation process is considered a serious drawback and limits the
implementation of these hydrogels in some pharmaceutical applications [14]. For
these reasons, various attempts had been devoted to the development of novel
cross-linking techniques that minimize the formation of these undesirable
byproducts. Among these techniques, photo-induced cross-linking is considered
one of the most efficient methods that employed in safe cross-linking and gelation.
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The convenient photo-crosslinking process includes the functionalization of the
main polymeric chain with polymerizable vinyl moieties such as maleic anhydride
or acrylate derivatives. Then, the cross-linking reaction will be performed by
irradiation to UV or visible light in presence of a suitable photo-initiator [19].
Although the obvious better results obtained from this technique compared to the
ordinary chemical cross-linking methods, the difficulty to remove the unreacted
photo-initiator in addition to trace initiator byproduct still could restrict the
employment of these hydrogels in some applications [20, 21].
In this work we describe an efficient method for the synthesis of a novel
modified photo-crosslinkable CMC. In the beginning, CMC was oxidized with
sodium periodate, which selectively cleave the C2-C3 bond and form modified
dialdehyde CMC [22]. Then, the resulted aldehyde groups were reacted with
cinnamic acid hydrazide in order to introduce the photo-active cinnamate moieties
onto the CMC backbone. The gelation of the obtained cinammate modified CMC
(CMC-CM) was performed upon irradiation in the UV region as a result of the
dimerization of the active cinnamate units via [2 +2π] cycloaddition reaction
[23].The obtained polymeric materials were extensively characterized using
Fourier transform infrared (FTIR), Nuclear magnetic resonance (1HNMR), wide
angle X-ray diffraction (XRD) spectra in addition to Scanning electron microscope
(SEM).
2. Materials and methods
2.1. Materials
Carboxymethyl cellulose(CMC) sodium salt (degree of substitution 2.34,
and Mw=7.6×105molg−1) was obtained from Sigma-Aldrich (USA), sodium
periodate, hydrazine hydrate, cinnamoyl chloride, cellulase (chromatographically
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purified, T. reese) and ephedrine hydrochloride were all supplied from Alfa Aesar
(USA). The other chemicals were of analytical grade and used as supplied without
any further treatments.
2.2. Periodate oxidation of CMC
The modified dialdehyde CMC (DCMC) was prepared according to the
procedures proposed by Li et al [1]. Three different samples with different
oxidation extents were prepared as explained in the following; In three 250 mL
conical flasks 100 mL 5%(w/v) aqueous CMC solutions were prepared, the pH3
was adjusted using acetic acid then the flasks were placed in a shaker fitted with
o
water bath adjusted at 35 C. To each flask we added 10 mL aqueous sodium
metaperiodate solution with concentrations 5.0 mM, 7.5mM and 10 mM and the
reaction continued for 4h. The oxidized DCMC samples with different aldehyde
contents were then precipitated by adding excess acetone then filtered and washed
with water/ethanol and finally with dimethyl formamide (DMF).
2.3. Determination of aldehyde content
For evaluation of the extent of periodate oxidation, the formed aldehyde
groups were estimated by turning it into oxime groups through reaction with
hydroxyl amine hydrochloride and titration of the released HCl against
standardized NaOH solution [24]. In details, 25mL 2%(w/v) aqueous DCMC
solution was adjusted to pH5 and allowed to react with 20mL 0.75M aqueous
o
NH2OH.HCl solution for 4h at 40 C. The released HCl was then estimated by
titration against 0.1M NaOH. Another blank sample was prepared and treated with
the same manner but using CMC. Eq. (1) was employed for determination of the
aldehyde content (Ald%).
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where MNaOH is the molar concentration of NaOH solution (0.5M), VC is the
consumed volume of NaOH in case of DCMC samples, Vb is the volume of
consumed NaOH for the blank CMC and m is the weight of the polymeric samples.
The obtained oxidized CMC samples with aldehyde contents 23%, 47% and
56% are named DCMC1, DCMC2 and DCMC3 respectively.
2.4. Synthesis of cinnamic acid hydrazide (CMH)
1g cinnamoyl chloride was added to 5mL acetonitrile and the mixture was
magnetically stirred till clear solution was obtained. The solution was then poured
dropwise into a round bottomed flask containing 2mL hydrazine hydrate. The
reaction mixture was magnetically stirred in ice bath. After 15 min, the white CMH
precipitate was filtered and washed with acetonitrile and ethanol.
2.5. Synthesis of photo-crosslinkable CMC-CM
The previously prepared DMF wet DCMC samples were placed in round
bottomed flasks and to which 20mL 2% CMH solution in DMF were added. The
flasks were then fitted with a reflux condenser and reflux continued in dark under
o
heterogeneous condition at 120 C with magnetic stirring. After 2h, the modified
polymeric samples were removed from the reaction mixture and washed with DMF
to extract any unreacted CMH then dried in an oven for 24h at 40 oC. The obtained
three photo-crosslinkable samples that derived from DCMC1, DCMC2 and
DCMC3 were respectively named CMC-CM1, CMC-CM2 and CMC-CM3.
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2.6. Photo-crosslinking
The photo-crosslnking process was carried by UV irradiation of 5% aqueous
CMC-CM solutions in quartz tubes utilizing high pressure 200W mercury UV
lamp at 360 nm for a desired period of time. The obtained gel discs were then
soaked in distilled water for 24h at room temperature in order to extract the
unreacted polymeric materials then removed and weighed. The gel were then dried
under vacuum and weighed again. Eqs. (2) and (3) were then employed to estimate
both gelation efficiency (GE) and degree of swelling (SD).
where Wsolid, Wdry and Wwet are the weights of CMC-CM, dry cross-linked CMC-
CM and wet cross-linked CMC-CM, respectively. Schematic presentations for both
synthesis and photo-crosslinking process are shown in Scheme 1.
Scheme 1
2.7. In-vitro Enzyme degradation
The enzymatic bio-degradation of the photo-crosslinked CMC-CM
hydrogels were performed by allowing 0.1g of the dry hydrogel to swell in 20mL
acetate buffer at pH5 for 24h. 1mL of the cellulase enzyme solution in the same
acetate buffer (10 units/mL) was then added and the reaction was incubated at 37
oC. After predetermined time periods, 0.25 mL aliquot was taken and replaced with
equivalent cellulase solution in order to estimate the amount of the reduced sugar
using dinitrosalicylic acid method [25]. Eq. (4) was utilized for evaluation of the
biodegradability.
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where Ms and Mb is the moles of the anhydro glucose units originally in the CMC
and in the solution after cellulase degradation.
2.8. Ephedrine hydrochloride loading and in-vitro release
The drug model ephedrine hydrochloride and the photo-crosslinkable CMC-
CM were mixed with ratio 30 mg/g. The mixture was dissolved in double distilled
water till clear homogeneous solution, which was then irradiated in the UV region
for 1h. The cross-linked ephedrine loaded hydrogel was then removed, washed
o
with distilled water and placed in the in-vitro release PBS medium at 37 C and
shacked at 50 rpm. Each hour, an aliquot from the PBS solution was withdrawn to
estimate the molar concentration of the released ephedrine utilizing UV–vis
spectroscopy. The absorbances estimated at 257 nm against a calibration curve of
ephedrine in the same buffer solution at pH 7.2 and 37 oC.
2.9. Instrumentation
Elemental analysis in all the modification steps was performed using
Perkin–Elmer 240 C Elemental Analytical Instrument (USA). Fourier transform
infrared spectra (FTIR) of the polymeric samples were carried out using a Perkin–
Elmer spectrophotometer with ATR accessory. Oxford NMR instrument (Model
Unity Inova 500 MHz, USA) was employed to obtain the 1H and 13C NMR spectra
of the modified samples.
The progress of the photo-crosslinking reaction in addition to the ephedrine
release from the cross-linked hydrogel was monitored using Perkin–Elmer Bio
UV–visible spectrophotometer. X-ray diffraction (XRD) spectra of the native
CMC, DCMC and CMC-CM before and after photo-crosslinking were performed
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using X-ray powder diffractometer (Japanese Dmax-rA, wavelength = 1.54 Ả,
CuKα radiation). The samples were scanned from 2θ = 5–70o, in step of 0.02o
using generator intensity of 40 kV and generator current of 50 mA. Scanning
electron microscope (SEM) examinations were performed using FEI Quanta-200
scanning electron microscope (FEI Company, The Netherlands). The hydrogel
samples were first allowed to swell in distilled water for 24h at room temperature.
Then, the swollen hydrogels were freeze-dried before visualizing under the
electron microscope.
The rheological characterization of CMC-CM before and after photo-
gelation was performed using ARES rheometer (TA Co., USA). Both storage and
loss moduli had been estimated as a function of frequency under oscillatory shear
at a strain of 0.5%.
3. Results and discussions
3.1. Sample characterization
Elemental analysis data of the start material CMC and its obtained
derivatives upon each modification step were collected in Table 1. As can be
observed, the presence of nitrogen in the prepared CMC-CM samples indicated the
successful Schiff base formation between the active –NH2 of the cinnamic acid
hydrazide and the aldehyde groups formed after periodate oxidation. Moreover, the
nitrogen percentage displayed a significant increase with increasing the Ald%
values related to the used DCMC. This of course could be attributed to the high
availability of the aldehyde groups to which the hydrazide units can interact. The
estimated degree of cinnamate functionalization was 1.2, 2.1 and 3.2 mmol/g for
CMC-CM1, CMC-CM2 and CMC-CM3 respectively.
Table 1
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The FTIR spectra of CMC, DCMC and CMC-CM2 are displayed in Fig.1.
The formation of the aldehyde groups upon periodate oxidation was clearly
confirmed by the existence of the characteristic -CHO peaks at about 1730 and 885
cm-1 in the DCMC spectrum (Fig.1b). Furthermore, the spectrum of CMC-CM2
(Fig.1c) confirmed the insertion of the cinnamate units through the Schiff base
formation by the appearance of the new signals at approximately 1650, 1580, 1275
and 750 cm-1, which are related to C=N, C=C, N-N and aromatic C-H respectively.
Figure 1
NMR spectra were also employed in evaluation of the CMC chemical
modification process. Fig. 2 presents the 1H NMR spectra of CMC, DCMC and
CMC-CM2. As can be seen in Fig. 2b, the formation of the aldehyde groups was
revealed by the appearance of the singlet signal at δ 9.72 ppm, which is
characteristic for the H-C=O proton beside the diagnostic C-H and O-H multiple
signals at approximate range δ 3.2-4.1 ppm. On the other hand, the incorporation
of the cinnamate moieties was evidenced from the spectrum of CMC-CM2 (Fig.
2c) by the presence of the doublet-doublet signals at δ 6.89-7.37 ppm
corresponding to trans cinnamate protons, doublet-doublet-triplet signals at δ 7.62-
7.38-7.33, which are related to the aromatic protons and singlet signal of –NH-
proton at δ 12.04.
Figure 2
13
In addition, C NMR spectra (Fig.3) reveal the periodate oxidation by the
presence of the aldehyde carbon signal at 200 ppm (Fig. 3b). On the other hand,
the spectrum of CMC-CM2 (Fig.3c) displayed new signals at 168 ppm related to
the hydrazide C=O group, 188, 145 ppm related to the cinnamate C=C and 127,
128 ppm related to the carbons of the aromatic ring. These results confirmed the
successful modification of the DCMC by incorporation of the photo-active
cinnamate moieties. Furthermore, the degree of functionalization was estimated by
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comparing the integral values of the characteristic cinnamate signals to that of C1
and the obtained results were in a good match with that obtained from the
elemental analysis.
Figure 3
3.2. Photo-crosslinking
The initiator- free photo-crosslinking reaction of the cinnamate modified
CMC-CM2 was investigated by UV irradiation of a thin film using 200W mercury
UV lamp at 360 nm. The UV spectrum of the film was examined after
predetermined time intervals and the results were presented in Fig. 4. As can be
noticed, the characteristic cinnamate absorption band at 315 nm [26] exhibited an
obvious lowering in intensity by increasing the UV irradiation time. In 30 min, the
intensity of the band decreased by approximately 50%. These results indicated that
the photo-crosslinking reaction was performed through the well known concerted
[2π+2π] cyclo-addition reaction of the photo-active cinnamate moieties, which
resulted in cyclobutane rings connecting the polysaccharide chains together in a
three-dimensional cross-linked network structure as shown in Scheme 1.
Figure 4
For more understanding of the photo-crosslinking process, geometry
optimization of the cinnamate modified CMC units before and after the [2π+2π]
cyclo-addition photo-reaction was carried out using MM+ force field in
HyperChem software version 8.03. The most stable conformation model is
presented in Structure 1a and as can be observed, the cinnamate moieties are
arranged away from each other providing a suitable position for approach with
minimum steric hindrance and consequently formation of the cross-linked network
as shown in Structure 1b.
Structure 1
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Furthermore, the kinetic studies were performed by calculating the extent of
cross-linking (ρt) Eq. (5) [27].
where A0 is the initial absorbance intensity and At is the absorbance at time t.
Fig. 5a displayed the change of the ρt as a function of time. The obtained
kinetic data exhibited the best linear fit with the second order integral relationship
(Eq. (6)), which obtained by plotting the non-crosslinking (%) (1/100-ρt) against
the irradiation time (t) [23]. As can be seen in Fig. 5b, the estimated rate constant
was 1.58x10-4 %-1min-1. These results revealed that the cross-linking process was
performed through the bimolecular second order [2π+2π] cyclo-addition reaction.
Figure 5
The influence of oxidation and each subsequent modification step was
examined utilizing XRD spectra. As presented in Fig. 6 the spectrum of native
unmodified CMC (Fig. 6a) exhibited an intense peak at 2θ = 22.70, which indicate
the semi-crystalline pattern of the polysaccharide chain. Upon periodate oxidation
and further incorporation of the cinnamic acid hydrazide units, the intensity of the
crystalline peak displayed a significant decrease as a result of the packing
destruction due to the cleavage of some glucopyranoside units [1, 24]. In addition,
the spectrum of the photo-crosslinked CMC-CM2 (Fig. 6d) exhibited an almost
amorphous pattern, which can be explained as a result of the formation of three
dimensional cross-linked matrixes and cleavage of the hydrogen bonding that hold
and organize the crystalline segments of the polysaccharide chain.
Fig. 6
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The Influence of the photo-crosslinking density on the morphological
structure of the obtained hydrogel was examined by visualizing scanning electron
microscope images of the freeze-dried hydrogels obtained from CMC-CM1 and
CMC-CM3 (Fig.7). Both images exhibited a sponge like porous texture. However,
the hydrogel derived from the highly functionalized CMC-CM3 exhibited
relatively smaller pores size with more compact structure, which could be
explained as a result of the higher cross-linking density.
Fig. 7
3.3. Gelation and swelling studies
The gelation efficiency (GE) of both CMC-CM1 and CMC-CM3 was
studied as a function of the irradiation time and the results were shown in Fig. 8a.
As can be noticed, in a time range from 10 to 60 min, the GE displayed an obvious
increase from 12.86 to 39.43% in case of CMC-CM1 and from 20.23 to 74.54% in
case of CMC-CN3. This observed high GE values obtained with the highly
functionalized CMC-CN3 could be attributed to the high availability of the inserted
photo-active cinnamate units, which is essential in the UV-induced photo-
crosslinking via [2π+2π] cyclo-addition reaction.
Also, the effect of irradiation time as well as the cinnamate content on the
swelling degree (SD) was investigated (Fig.8b). As can be seen, for both CMC-
CM1 and CMC-CM3, the SD exhibited a significant decrease by increasing the
UV irradiation time. On the other hand, the hydrogel derived from the highly
functionalized CMC-CM3 presents a lower SD compared to the CMC-CM1 with
the relatively lower cinnamate content. Generally, the hydrogels exhibited low SD
values by increasing the cross-linking density of their matrix network, which could
be achieved by increasing either UV-irradiation time or cinnamate content.
Fig. 8
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3.4. Rheological properties
In these experiments, aqueous CMC-CN2 solution was examined before and
after the photo-crosslinking performance for 30 min. Fig. 9 displayed the
dependence of both storage (G\) and loss modulus (G\\) on the angular frequency.
As can be seen, the uncross-linked sample exhibited a viscous state with
viscoelastic properties, which restrict the accurate measurements of both (G\) and
(G\\) values. On the other hand, upon photo-crosslinking process, within the whole
studied frequency range, G\ was greater than G\\. In addition, G\ was almost
constant and slightly increased by increasing frequency. These results revealed that
the CMC-CN2 solution exhibited semi-solid properties upon UV-irradiation, which
could be explained as a result of the photo-induced cyclo-addition reaction of the
inserted cinnamate units.
Furthermore, the storage modulus was also examined as a function of
frequency for both CMC-CM1 and CMC-CM3 in order to investigate the influence
of functionalization degree on the mechanical properties. As can be seen in Fig 9c,
the highly functionalized CMC-CM3 displayed higher G\ values compared that of
CMC-CM1 with lower cinnamate content. This of course could be explained as a
result of the formation highly cross-linked structure with more compact dense
texture matrix.
Fig. 9
3.5. Enzymatic degradability
The bio-degradation studies were performed by incubating the studied
o
hydrogel with cellulase enzyme at 37 C. The influence of the incubation time on
the degradation process is displayed in Fig. 10. Within three days, the hydrogel
derived from CMC-CM1, CMC-CM2 and CMC-CM3 exhibited approximate
degradation percents of 70, 48 and 34%, respectively. Moreover, the rate of the
enzymatic degradation showed an obvious decrease by increasing the cinnamate
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content. These observations could be explained as a result of chemical change
takes place upon cinnamate insertion and subsequent photo-crosslinking process,
which will of course restrict the substrate-enzyme interaction.
Fig. 10
3.6. In-vitro release studies
The potential of the prepared CMC-CM photo-cross-linkable polymeric
materials as a polymeric matrix for drug delivery systems was examined using
ephedrine as a drug model. The sustained release profiles of the entrapped
ephedrine from the cross-linked network of both CMC-CM1 and CMC-CM3 at pH
7.2 and at 37 oC were displayed in Fig. 11. As can be notice, ephedrine exhibited a
slower release from the more functionalized CMC-CM3 cross-linked matrix
compared to that observed from CMC-CM1. After 6 h the cumulative release of
ephedrine was approximately 15% and 28% from CMC-CM3 and CMC-CM1,
respectively. This observed slow release pattern with the highly functionalized
CMC-CM3 could be attributed to the high cross-linking density, which will limit
the drug diffusion out of the polymeric matrix and consequently decreases the rate
of the sustained release. These results were in a great agreement with some
previous reports [28, 29], which focused on the influence of the gelation degree on
the drug release profiles from the hydrogel polymeric matrixes. Usually, the drugs
exhibited a slower release profile from matrixes with smaller swelling degree,
revealing the importance of the cinnamate content on the release of ephedrine
release from the cross-linked CMC-CM matrices.
For more understanding of the mechanism by which ephedrine was released
from the studied cross-linked polymeric matrixes, the obtained data from the
release profile were fitted with the semi-emperical Korsmeyer–Peppas equation
(Eq. 6) [30].
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where k is a kinetic constant related to the structure and geometry of the polymeric
drug carrier, (n) is an exponent characteristic of the release mechanism, Mt and Mf
are the released ephedrine amounts at t and equilibrium, respectively.
The mechanism of ephedrine release from the polymeric network depends up
on the anticipated ‘n’ values. If n = 5, the release described as Fickian transport or
diffusion controlled mechanism (Case I), where the drug diffusion lower than the
polymeric relaxation [31, 32]. On the other hand, if n = 1 the drug release follows
the non-Fickian mechanism (Case II) in which the rate of polymeric network
relaxation lower than the rate of drug diffusion. If the n values lies between 0.5 and
1, the drug release mechanism is a combination of both diffusion and polymer
relaxation (anomalous case) [32]. The obtained n values from the kinetic pattern of
both CMC-CM3 and CMC-CM1 were 0.75 and 0.83, respectively, which may give
an evidence for non-Fickian anomalous transport kinetics related to both diffusion
and polymer relaxation release mechanism.
Fig. 11
4. Conclusion
A bio-combatable photo-active cinnamate modified CMC derivative was
manufactured and extensively characterized using various instrumental techniques.
Upon UV irradiation, the modified polymeric chains were cross-linked through the
[2π+2π] cyclo-addition interaction of the inserted cinnamte moieties. The photo-
crosslinking degree was found to significantly increase by increasing the degree of
cinnamate functionalization. In addition, gelation efficiency exhibited an obvious
increase accompanied by a significant decrease in swelling degree by increasing
the cross-linking density either by increasing the degree of cinnamate
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functionalization or by increasing the time of UV irradiation. Also, the obtained
hydrogel displayed an observed slower enzymatic biodegradation by increasing the
degree of cross-linking. The potential of the fabricated hydrogels was evaluated as
polymeric carriers in drug delivery systems using ephedrine hydrochloride as a
drug model and the results indicated the significant dependence of the release rate
on the cross-linking density of the polymeric hydrogel matrix.
Acknowledgement
The authors would like to acknowledge financial support for this work, from
the Deanship of Scientific Research, Taibah University Saudi Arabia, under grant
no. 6959/1436.
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Fig.1. FTIR spectra of (a) CMC, (b) DCMC and (b) CMC-CM2.
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Fig. 2. 1H NMR spectra of (a) CMC, (b) DCMC and (b) CMC-CM2 in D2O as solvent
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Fig. 3. 13C NMR spectra of (a) CMC, (b) DCMC and (b) CMC-CM2 in D2O as solvent
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Fig. 4. Changes in the UV spectral patterns of CMC-CM2 membrane after UVirradiation time t =
0, 5, 10, 15, 20, 25 and 30 min.
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( a)
40
30
20
10
0
0
5
10
15
20
25
30
Irradiation time (min)
0.016
0.015
0.014
0.013
0.012
(b)
y = 0.0111 + (1.58 x 10-4)x
R2 = 0.9923
0.011
0.010
5
10
15
20
25
30
Irradiation time (min)
Fig. 5. The effect of irradiation time onthe extent of CMC-CM-2 crosslinking (a) Linear second order
integral plot of the reciprocal of the percentage of theuncrosslinking against the time (b).
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Fig. 6. XRD crystalline patterns of CMC (a), DCMC (b), CMC-CM2 before (c) and after (d)
photo-crosslinking.
(a)
(b)
Fig. 7.SEM images of a cross-section of photo-crosslinked hydrogel derived from (a) CMC-
CM1and (b) CMC-CM3.
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80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
(a)
CMC-CM3
CMC-CM1
10
20
30
40
50
60
Irradiation time (min)
180
(b)
160
140
120
100
80
CMC-CM1
CMC-CM3
60
10
20
30
40
50
60
Irradiation time (min)
Fig. 8.Gelation efficiency as a function of irradiation time for aqueous solutions of CMC-CM
samples (a).The swelling degree as a function of irradiation time for the CMC-CM
hydrogels (b).
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Fig. 9.Dynamic storage and loss moduli of aqueous CMC-CM2 solution (a) before and (b) after
UV irradiation. (c) Storage modulus as a function of frequency for both CMC-CM1 and
CMC-CM3.
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70
60
50
40
30
20
10
CMC-CM1
CMC-CM2
CMC-CM3
0
10
20
30
40
50
60
70
80
Incubation time (h)
Fig. 10. In vitro biodegradation of two CMC-CM hydrogels incorporated with variouscinnamate
contents in (10 units/mL) cellulase solution of pH 5 at 37 ◦C.
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