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Carbohydrate Polymers
journal homepage: www . elsevier . com/locate/carbpol
D. Sathya Seeli, M. Prabaharan
Department of Chemistry, Hindustan Institute of Technology and Science, Padur, Chennai 603 103, India
for colon-specific drug delivery. The structure
of GGO-g-PMAc hydrogel was characterized
abstra 1
by FT-IR, H NMR and X-ray diffraction
article info ct
(XRD) analysis. The swelling degree of the
GGO-g-PMAc hydrogel at pH 7.4 was found
Article history: A novel type to be higher than that at pH 1.2. The drug
Received 12 August 2016 of ethylene release studies performed in pH 7.4 and 1.2
Received in revised form 9 November 2016 Accepted 30 glycol
November 2016 buffer solutions at 37 C revealed that the
dimethacrylate
Available online 2 December 2016 (EGDMA) rate and amount of drug released from the
cross-linked GGO-g-PMAc hydrogel at pH 7.4 were higher
Keywords: guar gum than that at pH 1.2. The MTT assay revealed
Guar gum oleate-graft- that there is no notice-able cytotoxicity of
Hydrogel poly(methacryl GGO-g-PMAc hydrogel at the concentration
Colon ic acid) (GGO- range of 0100 g/ml against the mouse
Controlled release g-PMAc) mesenchymal stem cell line (C3H10T1/2).
Cytotoxicity hydrogel was These results suggested that GGO-g-PMAc
prepared as a hydrogel can be a prospective pH-sensitive
pH-responsive carrier for colon-targeted drug delivery.
controlled
release carrier 2016 Elsevier Ltd. All rights reserved.
consi gradability, The o
i
dered hydrophilicity and non-difficulties
.
as toxic nature (Mishra,involved in the o
potent Yadav, Mishra, &oral colon drug r
1. Introduction
ial Behari, 2011;delivery are g
materi Prabaharan, 2011;absorption and /
Guar gum is a naturalals for Subhraseema &the degradation 1
polymer which is obtainedbiome Usharani, 2015; Yadav,of 0
from the seeds of Cyamopsisdical, drug .
Sand, Mishra, &molecules in the 1
tetragonolobus (Deepak,phar Behari, 2010; Yadav,
upper 0
Sheweta, & Bhupendar,mace Srivastav, Verma, & 1
2014). It is a non-ionicuti-cal Behari, 2013). Due to 6
galactomannan comprisingand the vul-nerability to 1 /
of 80% galactoman-nan,enviro Corresp
onding author. j
microbial degradation E-mail address:
12% water, 5% protein, 2%nment mprabaharan@y .
in the colon ahoo.com (M. c
acidic insoluble ash, 0.7%al environment and Prabaharan). a
ash and 0.7% fat. Theapplic stability over a wide pH r
backbone of guar gum is aations range, guar gum based b
linear -d-(14) linkeddue to materials haveh p
mannose units having -d-their capability to be usedt o
galactopyranose unitsbioav l
for colon-targeted drugt .
connected by (16) linkagesailabili p
delivery through the: 2
(Panariello, Favaloro,ty, oral administration/ 0
Forbicioni, Caputo, &bioco (Elias, Anil, Ahmad, &/ 1
Barbucci, 2008). In recentmpati Daud, 2010; Madan etd 6
years, guar gum and itsbility, al., 2014; Sathya Seelix
.
derivatives are widelybiode 1
& Prabaharan, 2016). . 1
d
.0 colon-specific drugand practical improved
92 delivery carriers suchapplications (Yihong, Huiqun,
01
as time-dependent(Nazar & & Chaobo,
44 gastro
- delivery carriers, pH-Umbreen, 2014; 2007).
intesti dependent deliverySathya Seeli, In this work,
86
nal carriers and bacteria-Dhivya,
17 EGDMA cross-
/ (GI) dependent deliverySelvamurugan, linked GGO-g-
20 tract carriers have been
& Prabaharan, PMAc hydrogel
16 that devel-oped (George & was prepared as
El lead 2016). Due to
se
Abraham, 2007; a colon-targeted
to the presence of
vie Kuntal, Tejraj, & drug delivery
syste weakly acidic
r Anandrao, 2011; carrier by
mic groups, the pH-
Lt Susan, Ellen, Jennifer, grafting PMAc
d. side dependent
& Simon, 2015; onto GGO in the
All effect delivery carriers
Wakerly, Fell, Attwood, presence of
rig s and can present the
ht
& Parkins, 1997). EGDMA as a
low limited swelling
s These carriers can cross-linking
bioav behavior in the
re deliver the drug more agent and
ailabili acidic stomach
se specifi-cally to the potassium
rv ty of fluid, which limits
colon site due to their persulfate as a
ed the the drug release
physicochemical free radical
. drug from the carriers.
properties and thereby initiator. The
in the However,
improve the GGO-g-PMAc
colon because of the
bioavailability and hydrogel is
site. increased pH in
absorption of drugs for expected to
To the large
the potential provide a pH-
overc intestine and
therapeutic effects. responsive
ome colon
However, among the character and
these environment, the
drug deliv-ery carriers, sus-tained
drawb extent of
in recent years, pH- release of the
acks, swelling and
dependent delivery loaded
variou thereby the
carriers have attracted hydrophobic
s amount of drug
increasing attention drug due to the
types release from the
because of their presence
of hydrogel will be
desirable properties
52 D.S. Seeli, M. Prabaharan / Carbohydrate Polymers 158 (2017) 5157
Table 1
Reaction conditions for the preparation of GGO with different DS values.
Types of GGO Guar gum (mmol) Oleic acid (mmol) DMAP (mmol) Guar gum/oleic acid (mmol) DS Yield (%)
GGO1 2.056 2.056 2.056 1:1 0.23 74
GGO2 2.056 10.28 10.28 1:5 0.33 53
GGO3 2.056 20.56 20.56 1:10 0.5 59
was efficiently utilized
4 2 by the available free
into a concentration of 3 10 /cm in 24 wellradical sites on GGO
plates and incu-bated for a period of 12 h.to produce the grafted
Thereafter, the cells were treated with GGO-g- product.
PMAc hydrogel at different concentrations (0, 10,
30, 50, 100 and 150 g/ml) for 24 h. The control
cells were left untreated and the positive control
cells were treated with 0.1% Triton-X 100. 3.2. Characterization
Thereafter, after washing with phosphate bufferof GGO and GGO-g-
solution (PBS), the cells were treated with 5 mg/ml PMAc hydrogel
of MTT solution at 37 C for 4 h. Then, the culture
The FT-IR
medium was removed and 0.2 ml of DMSO was spectrum of guar gum
incorporated with the precipitates. The absorbance presents a broad OH
value of result-ing solution was measured at 570stretch absorption
band in between 3600
nm using a spectrophotometer. Using SPSS 1
software, statistical analysis was performed by and 3000 cm and
the aliphatic C H
one-way ANOVA followed by StudentNewman stretch in between
Keuls test. Inconsistencies with a P value < 0.05 2930 and 2890 cm1
were regarded as statistically significant. as revealed in Fig. 1A
(Mishra & Goutam, Fig. 1. FT-IR spectra of (A)
2011). The other major guar gum, (B) GGO, and
3. Results and discussion absorption bands at (C) GGO-g-PMAc hydrogel.
1
1015 and 877 cm
3.1. Synthesis of GGO-g-PMAc hydrogel correspond to C O C
stretching vibrations of
glycosidic linkages. trum of GGO (Fig. 1B),
To prepare GGO-g-PMAc hydrogel, first GGOThe absorption bands in addition to the
with different DS values were prepared by reactingin between 1225 and characteristic peaks of
1 guar gum, the new
guar gum aqueous solution with the required817 cm correspond
amounts of oleic acid in the presence of DMAP as to the highly coupled peaks at 1735, 2921,
C C O, C OH and C O 2853, 1435 and 1383
listed in Table 1. The reaction route for the C stretching modes of
1
synthesis of GGO is shown in Scheme 1. Toguar gum backbone. cm were observed.
determine the DS of the oleic acid group in GGO,In the IR spec- A peak at 1735 cm
1
Fig. 3 shows the XRD pattern of guar gum, GGO, and GGO-g-
PMAc hydrogel. As shown in Fig. 3A, guar gum shows the
characteristic diffraction peaks at 17.47 and 20.12 due to its semi-
crystalline in nature (Deepak, Sheweta, & Khatkar, 2012). In the case
of GGO (Fig. 3B), in addition to the characteristic diffraction peaks of
guar gum, a new peak was also observed at 14.54 . Moreover, the
intensity of diffraction peaks at 17.47 and 20.12 was considerably
increased. This observation indicates that the crystallinity of guar gum
was enhanced to some extent after the chemical modifica-tion with
oleic acid due to the ordered arrangement of the grafted polymer
chains. In the diffraction pattern of GGO-g-PMAc hydrogel (Fig. 3C),
the crystalline peaks of GGO were disappeared and new characteristic
amorphous halo peaks of PMAc observed at 16 and 32 (Guangping,
Siqi, Jingquan, Zhen, & Qinglin, 2014). This obser-vation might be due
to the destruction of original semi-crystalline structure of GGO when
grafting with PMAc. This result indicated that the PMAc has been
grafted effectively onto GGO back bone.
1
Fig. 2. H NMR spectra of (A) guar gum, (B) GGO, and (C) GGO-g-PMAc hydrogel.
D.S. Seeli, M. Prabaharan / Carbohydrate Polymers 158 (2017) 5157 55
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