Journal of Biomaterials and Nanobiotechnology, 2011, 2, 36-40
doi:10.4236/jbnb.2011.21005 Published Online January 2011 (http://www.SciRP.org/journal/jbnb)
Pectin-Based Biodegradable Hydrogels with
Potential Biomedical Applications as Drug
Delivery Systems
Mohammad Sadeghi
Department of Chemistry, Science Faculty, Islamic Azad University, Arak Branch, Arak, Iran
Received October 28th 2010; November 23rd 2010; November 30th 2010.
ABSTRACT
In this work, synthesis and swelling behavior of a superabsorbent hydrogel based on Pectin (Pc) and polyacrylon itrile
(PAN) were investigated. A mechanism for hydrogel formation was proposed and the structure of the product was es-
tablished using FTIR spectroscopy. The Pc-poly (sodium acrylate-co-acrylamide) hydrogel exhibited a pH-responsive
swelling-deswelling behavior at pH’s 2 and 8. This on-off switching behavior provides the hydrogel with the potential
to control delivery of bioactive agents. Release profiles of ibuprofen (IBU), a poor water-soluble drug, from the hy-
drogels were studied under both simulated gastric and intestinal pH conditions.
Keywords: Pectin, Polyacrylonitrile, Hydrogel, Ibuprofen, Drug Delivery
1. Introduction
Pectin is a naturally occurring biopolymer that is finding
increasing applications in the pharmaceutical and
biotechnology industry. It has been used successfully for
many years in the food and beverage industry as a
thickening agent, a gelling agent and a colloidal stabilizer.
Pectin also has several unique properties that have
enabled it to be used as a matrix for the entrapment and/or
delivery of a variety of drugs, proteins and cells.
Furthermore, crosslinked polymers from Pectin can form
hydrogels that are able to absorb and retain hundreds of
times their weight of water and are known as superabsor-
bents [1]. The properties of these hydrogels have attracted
the attention of many researchers and technologists and
have found wide-spread applications in many fields, such
as drug delivery systems, agriculture, separation processes
[2-5]. The combination of the hydrophilic acrylic polymer
properties with the biodegradable character of Pectin
based blends, will lead to interesting hydrogels with po-
tential applications as biomaterials exhibiting different
properties depending on the composition and on the type
of interactions within the network, attending to chemical
crosslinking and hydrogen bonding interactions [6]. This
work deals with the development of new biodegradable
hydrogels developed by the polymerization of AN and
some formulations with sodium hydroxide as crosslinker,
in the presence of Pectin.
2. Experimental
2.1. Hydrogel Preparation
A one step preparative method was used for synthesis of
Pc-poly(sodium acrylate-co-acrylamide)hydrogel, Pc-poly
(NaAA-co-AAm), hydrogel. Pectin (1.33 g) was added to
35 mL of doubly distilled water in a three-neck reactor
equipped with a mechanical stirrer (Heidolph RZR 2021,
three blade propeller type). The reactor was immersed in
a thermostated water bath. After complete dissolution of
the Pectin, sodium hydroxide (10.0 wt %) was added to
the Pectin solution at desired temperature (alkalization
temperature, 80˚C). The mixture was allowed to stir for
certain times (alkalization times, 120 min). The various
amount of polyacrylonitrile (1.0 g) was dispersed in the
reaction mixture to saponify for certain times and tem-
peratures (alkaline time and temperature). During the
saponification NH3 gas was evolved and a color change
from red to light yellow. This discoloration was an indi-
cation of the reaction completion. The pasty mixture was
allowed to cool to room temperature and neutralized to
pH 8.0 by addition of 10 wt % aqueous acetic acid solu-
tion. Then the gelled product was scissored to small

Pectin-Based Biodegradable Hydrogels with Potential Biomedical Applications as Drug Delivery Systems 37
pieces and poured in ethanol (200 mL) to dewater for 5 h.
The hardened particles were filtered and dried in oven
(50˚C, 10 h). After grinding, the powdered superabsor-
bent hydrogel was stored away from moisture, heat and
light.
2.2. Drug Loading Efficiency and In Vitro Drug
Release
Powdered samples (1 g ± 0.0001), with average particle
sizes between 40-60 mesh (250-420 µm), were accu-
rately weighted and immersed in an alkaline solution of
ibuprofen (IBU, 0.54 g dissolved in 50 mL distilled water)
at 0˚C for 25 h. The swollen hydrogels loaded with drug
were placed in a vacuum oven and dried under vacuum at
37˚C. The loading amount of drug in the hydrogels was
calculated from the decrease in the concentration of the
IBU solution which was determined using a UV spec-
trophotometer (UV-1201, Shimadzu, Kyoto, Japan). The
loading efficiency of the Pectin-based hydrogels was
calculated as the ratio of the final to the initial IBU con-
centration.
In vitro release was carried out in duplicate by incu-
bating 0.01±0.0001 g of the IBU-loaded hydrogels into a
cellophane membrane dialysis bag (D9402,
SIGMA-ALDRICH) in 50 mL of buffer solution (either
pH 1.2 or 7.4) at 37˚C. At specific time intervals, 1 mL
aliquots of sample was withdrawn and after suitable dilu-
tion the concentration of drug released was measured by
UV spectrophotometer. The drug release percent was
calculated twice using the following equation:
Released drug (%) =Rt/L×100 (1)
where L and Rt represent the initial amount of drug
loaded and the final amount of drug released at time t.
3. Results and Discussion
3.1. Mechanism of Hydrogel Formation
A general reaction mechanism for Pc-poly(NaAA-co-
AAm) hydrogel formation is shown in Scheme 1. In the
first step, Pectin hydroxyl groups were converted to cor-
responding alkoxides using sodium hydroxide. These
macroalkoxides initiated a crosslinking reaction between
adjacent polyacrylonitrile pendant chains forming
naphthyridine cyclic structures (including imine, -C=N-,
conjugated bonds with deep red color). The intermediate
was then hydrolyzed using residual sodium hydroxide
aqueous solution to produce hydrophilic carboxamide
and carboxylate groups (Scheme 1) with a resulting color
change from red to light yellow. This sharp color change
was used as an indication to halt the alkaline treatment.
However, incompletely hydrolyzed structures may also
give rise to a few crosslinking points result in a loosely
crosslinked network.
Infrared spectroscopy was carried out to confirm the
chemical structure of the materials obtained. The FTIR
spectra of Pc-PAN physical mixture and the resulted hy-
drogel, Pc-poly(NaAA-co-AAm) are shown in Figure 1.
The band observed at 2242 cm-1 was attributed to
stretching of cyanide (Figure 1a). The Pectin backbone
with side chains with carboxamide and carboxylate fun-
ctional groups were identified by three new peaks at
1407, 1556, and 1675 cm-1 (Figure 1b).
These peaks were attributed to C=O stretching in car-
boxamide functional groups and symmetric and asym-
metric stretching modes of carboxylate groups, respect-
tively [7].
The in situ reaction was conducted with alkaline hy-
drolysis in absence of the polysaccharide. The product
obtained was soluble, indicating that crosslinks were not
being formed without Pectin. This substantiated the fact
that Pectin hydroxyls are involved in the crosslinking
process leading to the formation of hydrogels.
3.2. PH-Reversibility for Pc-Poly (NaAA-co-AAm)
Hydrogel
Since the hydrogels show different swelling behavior at
various pHs, we investigated their pH-reversibility in
solutions buffered at pH 2.0 and 8.0. A stepwise repro-
ducible in swelling change of the hydrogel at 25 ˚C with
alternating pH between 2.0 and 8.0 is seen in Figure 2.
At pH 8.0, the hydrogel swelled up to 157 g/g due to
anion–anion repulsive electrostatic forces, while, at pH
2.0, it shrunk within a few minutes due to protonation of
carboxylate groups. This sharp swelling–deswelling be-
havior of the hydrogels makes them suitable candidates
for controlled drug delivery systems. Such on-off swit-
ching behavior as reversible swelling and deswelling has
been reported for other ionic hydrogels [8-11].
Transmittance/Wavenumber (cm-1)
Figure 1. FTIR spectra of (a) the physical mixture of Pectin
and PAN and (b) the crosslinked Pc-poly (NaAA-co-AAm)
hydrogel.

Pectin-Based Biodegradable Hydrogels with Potential Biomedical Applications as Drug Delivery Systems 38
Scheme 1. Proposed mechanism for crosslinking during the hydrolysis of nitrile groups of the Pc–PAN mixture to produce
the Pc–poly (NaAA-co-AAm) hydrogel.
3.3. In vitro IBU Release in the Simulated
Human Gastrointestinal System
To determine the potential application of Pectin-based
superabsorbent containing a pharmaceutically active
compound, we have investigated the drug release behav-
ior IBU form this system under physiological conditions.
The percent of released drug from the polymeric carriers
as a function of time is shown in Figure 3.
The concentration of IBU released at selected time in-
tervals was determined by UV spectrophotometer. The
IBU-loaded hydrogels with high degrees of drug loading
(>80%) were prepared by the swelling-diffusion method.
The amount of IBU released in a specified time from the
Pectin-based hydrogel decreased as the pH of the disso-
lution medium was lowered, indicating better release in a
medium with a pH much higher than that of the stomach.
At low pH values, electrostatic repulsion between the

Pectin-Based Biodegradable Hydrogels with Potential Biomedical Applications as Drug Delivery Systems 39
0
20
40
60
80
100
120
140
160
180
0306090120 150 180 210
Swlling time, min
Swelling capacity, g/g
Figure 2. On-off switching behavior as reversible pulsatile
swelling (pH 8.0) and deswelling (pH 2.0) of
Pc-poly(NaAA-co-AAm) hydrogel. The time interval be-
tween the pH changes was 30 min.
0
20
40
60
80
100
120
0 10203040
Time, h
Released drug, %
p
H=7
pH=1
Figure 3. Release of IBU from hydrogel carrier as a func-
tion of time and pH at 37˚C.
carboxylic acid groups of backbone is low, thus de-
creases gel swelling and minimizes release of IBU via
diffusion. However, in alkaline media the presence of
OH⎯ increases the electrostatic repulsion between car-
boxylate groups, thus increases the gels swelling degree
and so the release of IBU was increased [12-13]. The
amounts of the loaded drug in superabsorbent hydrogels
was significantly affected by the loading time (Figure 4).
With increasing loading time, the amount of drug loaded
is initially increased and then begins to level off.
4. Conclusion
The superabsorbent hydrogel, Pc-poly(NaAA-co-AAm),
was synthesized through alkaline hydrolysis of Pc-PAN
physical mixture. The reaction of Pectin alkoxide anions
with nitrile groups of polyacrylonitrile, formed crosslinks
0
50
100
150
200
250
300
350
400
450
500
051015 2025 30
Time, h
mg loaded drug/g hydrogel
Figure 4. The depende ncy of the drug loading amount to the
loading time.
producing a three-dimensional network. No toxics mate-
rial were used in the synthesis, this practical approach
may be preferred to as a relatively "green process". This
one-step preparative method conducted under normal
atmospheric conditions in a short period of time. The
dark red-yellow color change provided a visual indica-
tion for the reactions progress. The superabsorbent hy-
drogels exhibited high sensitivity to pH, so that, the re-
versible swelling-deswelling behavior in solutions with
acidic and basic pH, contributes to the suitability of these
hydrogels as candidates for controlled drug delivery sys-
tems. In vitro drug-release studies in different buffer so-
lutions showed that the most important parameter affect-
ing the drug-release behavior of hydrogels is the pH of
the solution. The release value of Ibuprofen from hy-
drogels at pH 7.4 was higher than that at pH 1.2 due to
the electrostatic repulsion between carboxylate groups.
5. Acknowledgements
The author thanks the Research center of Islamic Azad
University of Arak.
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