International Journal of Diabetes Mellitus 2 (2010) 32–37

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International Journal of Diabetes Mellitus

journal homepage: ees.elsevier.com/locate/ijdm

Original Article

Dietary fiber psyllium based hydrogels for use in insulin delivery

Baljit Singh *, Nirmala Chauhan
Department of Chemistry, Himachal Pradesh University, Shimla 171 005, India

a r t i c l e i n f o a b s t r a c t

Article history: The present article is related to the development of psyllium based oral insulin delivery systems that
Received 27 August 2009 could release insulin in a controlled and sustained manner. Psyllium is a medicinally important gel, form-
Accepted 20 December 2009 ing glucose lowering dietary fiber and drug delivery system developed by its functionalization will have
the double potential of curing diabetes. Psyllium and acrylamide/methacrylamide based hydrogels were
prepared, and the effect of pH on the release dynamics of insulin from drug loaded hydrogels has been
Keywords: studied to evaluate the drug release mechanism. Non-Fickian diffusion mechanism has been observed
Drug delivery devices
for the release of insulin in the pH 7.4 buffer.
Hydrogels
Insulin
Ó 2009 International Journal of Diabetes Mellitus. Published by Elsevier Ltd.
Open access under CC BY-NC-ND license.
Diabetes mellitus

1. Introduction proteolytic degradation. In the basic and neutral environments of

Diabetes mellitus is a common problem nowadays which is
caused by decreased production of insulin or by decreased ability
to use insulin. This leads to an increase in blood glucose level.
Due to the inconvenience of the traditional treatment of diabetes
by subcutaneous administration of insulin injection, various
attempts have been made to develop an efficient method of insulin
delivery [1,2]. Usually, insulin is injected subcutaneously two to
four times to the patients in a day, because they need a relatively
constant basal level of insulin to achieve a near physiological pat-
tern of insulin secretion. Therefore, there has been significant
interest in the development of oral delivery systems for insulin
that could release the drug in a constant level for longer periods;
patients would be freed from the need to administer multiple
doses. Hydrogels have been shown to be promising candidates
for such a system [3,4].
The goal of oral insulin delivery devices is to protect the sensi-
tive drug from proteolytic degradation in the stomach and upper
portion of the small intestine. The pH responsive hydrogels have
been studied as potential drug carriers for the protection of insulin
from the acidic environment of the stomach, before releasing in the
small intestine. In one case, insulin was administered orally to
healthy and diabetic Wistar rats through pH responsive hydrogels.
In the acidic environment of the stomach, the gels remained un-
swollen due to the formation of intermolecular polymer complexes
and the insulin remained in the gel and was protected from
* Corresponding author. Tel.: +91 1772830944; fax: +91 1772633014.
E-mail address: baljitsinghhpu@yahoo.com (B. Singh).
the intestine, the complexes dissociated which resulted in rapid
gel swelling and insulin release. Within 2 h of administration of
the insulin-containing polymers, strong dose-dependent hypogly-
cemic effects were observed in both healthy and diabetic rats.
These effects lasted up to 8 h following administration [5]. In an-
other study, the ability of the insulin loaded hydrogels to influence
the blood glucose levels of the diabetic rats was investigated. The
blood glucose level has been reduced for animals that received
the insulin loaded hydrogel and the effect lasted for 8–10 h. It
was also observed, two capsules per day of the hydrogel micro-par-
ticles containing 80 I.U./kg of insulin dose were sufficient to control
the blood glucose level of fed diabetic rats between 100 and
300 mg/dl [6].
Insulin-loaded polymer micro-particles composed of cross-
linked poly(methacrylic acid) and poly(ethylene glycol) are
multi-functional carriers, and have shown high insulin incorpora-
tion efficiency, a rapid insulin release in the intestine, enzyme-
inhibiting effects and mucoadhesive characteristics. Thus, these
are potential carriers for insulin delivery via an oral route. Drug re-
lease from the hydrogel is affected by several factors, such as pore
size, degradability, size, hydrophobicity, the concentration of a
drug and the presence of specific hydrogel-drug interactions. Ini-
tially, the release mechanism from a biodegradable hydrogel is
limited by the drug’s diffusivity. Following this, a combination of
diffusion and degradation processes controls the drug’s release
from the polymeric matrix [7,8].
Polysaccharides based hydrogels enhance the intestinal absorp-
tion of insulin and increase the relative pharmacological bioavailabil-
ity of insulin; it has been investigated by monitoring the plasma
glucose level of alloxan-induced diabetic rats after oral administra-
tion of various doses of insulin-loaded chitosan-nanoparticles [9].

1877-5934 Ó 2009 International Journal of Diabetes Mellitus. Published by Elsevier Ltd. Open access under CC BY-NC-ND license.
doi:10.1016/j.ijdm.2009.12.014
 B. Singh, N. Chauhan / International Journal of Diabetes Mellitus 2 (2010) 32–37
On the other hand, the blood glucose level can also be controlled
by the polysaccharides, based diet management therapy. Accord-
ing to a report by the American Diabetic Association, fiber im-
proves the control of blood glucose, and delays glucose
absorption and hyperinsulinaemia [10]. Viscous forms of dietary
fiber have been shown to improve blood glucose control by trap-
ping ingested carbohydrates inside the viscous gel formed after
digestion. As a result, sugars are absorbed into the bloodstream
more slowly, limiting the rise in blood glucose seen after a meal
[11,12]. It has been suggested that the benefits of increased fiber
intake result principally from the greater consumption of soluble
forms, due to effects on gastric emptying, macronutrient absorp-
tion, and reduced postprandial glucose responses [13,14]. Insolu-
ble fiber may reduce diabetes risk by the production of short
chain fatty acids in the colon and their effect on hepatic insulin
sensitivity [15,16]. The advantages of high-fiber diets for diabetic
patients have also been said to include the lowering of serum lip-
ids, assisted weight reduction and maintenance, along with the
lowering of blood glucose levels [17,18]. Psyllium is one of the
medicinally important gel forming glucose lowering dietary fiber.
It reduces hyperglycemia in diabetes via inhibition of intestinal
glucose absorption and enhancement of motility [19]. Since the
glucose lowering effect of psyllium was clearly evident when
simultaneously administered with glucose, inhibition of glucose
absorption in the gut is a likely contributor to the mechanism of
action [20]. Psyllium in the diet also improves glucose tolerance
in diabetes [21,22]. This effect may be due to retarded gastric
emptying, increased intestinal transit, or a modification of the
secretion and action of digestive enzymes [23]. During the last
two decades, several studies have been carried out to investigate,
whether psyllium interferes with normal intestinal absorption of
carbohydrate in healthy volunteers [24] and in type 1 [25] and
type 2 diabetic patients [26]. The improvement in glucose toler-
ance produced by consumption of viscous fiber is due to slower
absorption of carbohydrates, rather than mal-absorption. Intimate
mixing, allowing physical interaction between food and fiber,
seems to be important in converting the carbohydrate to what
might be termed a slow-release form [27]. The mechanism of ac-
tion of gel forming fiber is related to the ability to increase the vis-
cosity of the gastrointestinal contents, and thus, interfere with
motility and absorption [28].
Psyllium mucilage obtained from the seed coat by mechanical
milling/grinding of the outer layer of the seeds and yield amounts
to approximately 25% of the total seeds yield. Mucilage is fibrous,
hydrophilic and forms the clear colorless mucilaginous gel by
absorbing water. The gel nature and composition of the polysac-
charides extracted from the seeds of the Plantago ovata has been
reported in literature. The gel forming fraction of the alkali-
extractable polysaccharides is composed of arabinose, xylose and
traces of other sugars. Beside its sugar lowering property, it has
been reported for the treatment of constipation, diarrhea, inflam-
mation bowel diseases-ulcerative colitis, obesity in children and
adolescents and high cholesterol [29].
In view of the pharmacological importance of psyllium polysac-
charides to reduce glucose absorption and drug delivery devices
based on hydrogels, psyllium, if suitably tailored to prepare the
hydrogels, can act as the double potential candidates to develop
novel drug delivery systems. Therefore, the present study is an
attempt to synthesize psyllium and poly(AAm) and poly(AAm-
co-MAAm) based hydrogels by using N,N0 -methylenebisacrylamide
(N,N-MBAAm) as crosslinker and ammonium persulfate (APS) as
initiator and thereafter use as drug delivery devices. It also dis-
cusses the in vitro release dynamics of insulin in a different release
medium, for the evaluation of release mechanism and diffusion
coefficients.
33
2. Experimental
2.1. Materials and method
Plantago psyllium mucilage (Psy) was obtained from Sidpur Sat
Isabgol factory (Gujrat, India), acrylamide (AAm) and methacryla-
mide (MAAm) were obtained from Merck-Schuchardt, Germany.
Sodium hydroxide, Sodium potassium tartrate and Folin’s reagents
was obtained from Merck Mumbai-India. Ammonium persulphate
(APS), copper sulphate and N,N0 -methylenebisacrylamide (N,N-
MBAAm) was obtained from S.D. Fine, Mumbai-India and were
used as received. Insulin was obtained from the Torrent Pharma-
ceuticals Ltd., Indrad, Mehsana, India. Sodium carbonate was
obtained from Ranbaxy, SAS Nagar Punjab-India.
2.2. Synthesis of polymers/hydrogels
Reaction was carried out with 1 g of psyllium husk, definite con-
centration of monomer, initiator and crosslinker taken in the aque-
ous reaction system at 65 °C temperature for 2 h. Polymers were
stirred for 2 h in distilled water and for 2 h in ethanol to remove
the soluble fraction and then were dried in oven at 40 °C. Two
types of hydrogels were prepared by using AAm and mixture of
AAm/MAAm. The hydrogels were named as psy-cl-poly(AAm)
and psy-cl-poly(AAm-co-MAAm) hydrogels, respectively. For the
synthesis of psy-cl-poly(AAm) hydrogels 7.03  101 mol/L of
AAm and was used along with 1.095  102 mol/L of APS,
16.20  103 mol/L of N,N-MBAAm. On the other hand, the
psy-cl-poly(AAm-co-MAAm) hydrogels was synthesized by taking
3.52  101 mol/L of AAm and 0.58  101 mol/L of MAAm simul-
taneously in the mixture containing 0.66  102 mol/L of APS and
9.73  103 mol/L of N,N-MBAAm. These hydrogels were used to
study the release dynamics of the drug from the drug loaded
hydrogels.
2.3. Release dynamics of insulin from drug loaded hydrogels
2.3.1. Preparation calibration curves
In this procedure, the absorbance of a number of standard solu-
tions of the reference substance at concentrations encompassing
the sample concentrations were measured on the UV Visible Spec-
trophotometer (Cary 100 Bio, Varian) and calibration graph was
constructed. The concentration of the drug in the sample solution
was read from the graph as the concentration corresponding to
the absorbance of the solution. Three calibration graphs of insulin
were made to determine the amount of drug release from the drug
loaded polymeric matrix respectively for distilled water, pH 2.2
buffer and pH 7.4 buffer [29].
2.3.2. Drug loading to the polymer matrix
The loading of a drug onto hydrogels was carried out by a swell-
ing equilibrium method. The hydrogels were allowed to swell in
the drug solution of known concentration for 24 h at 37 °C and
then dried to obtain the release device.
2.3.3. Drug release from polymer matrix
In vitro release studies of the drug were carried out by placing
dried and loaded sample in definite volume of releasing medium
at 37 °C temperature. The amount of insulin released was assayed
spectrophotometrically by Lowry method [30]. The absorbance of
the solution was measured at wavelength 768.0 nm, 753.0 nm
and 758.0 nm, respectively, for release in distilled water, pH 2.2
buffer and pH 7.4 buffer after every 30 min in each case. The pro-
cedure for the Lowry method is as follows.
34 B. Singh, N. Chauhan / International Journal of Diabetes Mellitus 2 (2010) 32–37
2.3.3.1. Reagents used for Lowry method. Reagent A: sodium carbon-
ate (2% w/v) in 0.1 N sodium hydroxide solution was prepared by
dissolving 20 g of sodium carbonate and 4 g of sodium hydroxide
in 1 L of distilled water.
Reagent B: copper sulphate solution (1% w/v) was prepared by
dissolving 1 g of copper sulphate (AR) in 100 mL of distilled water.
Reagent C: sodium potassium tartrate solution (2% w/v) was
prepared by dissolving 2 g of the salt in 100 mL distilled water.
Reagent D: alkaline copper reagent: 1 mL each of reagents B and
C was mixed with 98 mL of reagent A and vortexed. This reagent
was prepared freshly.
2.3.3.2. Procedure for Lowry method. To 1 mL of the standard pro-
tein solution containing 10–100 lg of protein or released insulin
sample solution were added 4 ml of reagent D and the contents
were mixed. After 10 min of incubation at room temperature,
0.4 mL of Folin’s reagent was added and the contents were vor-
texed immediately. A reagent blank with 1 mL of distilled water
(or buffer solution of respective pH) was also processed in same
manner as described above. After 30 min of incubation at room
temperature, the blue color developed was measured at kmax. The
calibration curve was constructed and computed to calculate the
concentration of the insulin released from the sample. While calcu-
lating the insulin concentration in the unknown sample, the dilu-
tion factor has been taken into account [30].
2.3.4. Preparation of buffer solution
Buffer solution of pH 2.2 was prepared by taking 50 mL of 0.2 M
KCl and 7.8 ml of 0.2 N HCl in volumetric flask to make volume
200 ml with distilled water. Buffer solution of pH 7.4 was prepared
by taking 50 mL of 0.2 M KH2PO4 and 39.1 mL of 0.2 N NaOH in vol-
umetric flask to make volume 200 ml with distilled water [31].
2.4. Mechanism of swelling and drug release from polymer matrix
The mechanisms of swelling and drug release have been dis-
cussed in detail in our earlier study [29]. Swelling of polymers
has been classified into three types of diffusion mechanisms, on
the basis of relative rate of diffusion of water into polymer matrix
and rate of polymer chain relaxation [32–35]. The values of diffu-
sion exponent ‘n’ and diffusion coefficients have been evaluated
for the swelling of the polymers and for the release of the drug
from the polymer. The values of diffusion coefficients have been
evaluated for the release of the drug from the polymer, and the re-
sults are presented in Table 1.
3. Results and discussion
Polymeric networks were synthesized by chemically induced
polymerization through free radical mechanism. APS has generated
the reactive sites, both on the psyllium and monomer, leading to
Table 1
Results of diffusion exponent ‘n’, gel characteristic constant ‘k’ and various diffusion coefficients for the release of insulin from drug loaded polymers in different medium at 37 °C.
Drug in releasing medium Diffusion exponent ‘n’ Gel characteristic constant ‘k’  102
Psy-cl-poly(AAm)
Distilled water 0.81 0.87
pH 2.2 buffer 0.38 8.39
pH 7.4 buffer 0.60 2.73
Psy-cl-poly(AAm-co-MAAm)
Distilled water 0.60 3.29
pH 2.2 buffer 0.40 10.69
pH 7.4 buffer 0.57 3.46
the propagation of the reaction. In the presence of crosslinker
N,N-MBAAm (CH2@CHCONHCH2 NHCOCH@CH2) four reactive sites
are generated and these sites can be linked both with the radical on
the psyllium and the poly(AAm)/poly(MAAm) and formed a cross-
linked three-dimensional networks, which have been used to study
the in vitro release of the model drugs.
3.1. Characterization
FTIR spectra of psyllium, psy-cl-poly(AAm) and psy-cl
poly(AAm-co-MAAm) polymers were recorded in KBr pellets on
Nicolet 5700 FTIR (THERMO) shown in (Fig. 1a–c). The broad
absorption bands at 3421.6 and 3415.6 cm1 were observed due
to –OH and NH stretching of –OH and NH groups present in psy-
cl-poly(AAm), and psy-cl poly(AAm-co-MAAm) polymers and FTIR
absorption bands due to C@O stretching of amide has been prom-
inently witnessed at 1664.3 and 1664.8 cm1 for respective poly-
mer matrix. The bands at 1042.3 and 1041.9 cm1 were observed
due to C–N stretching of amide present in all the three modified
samples apart from usual peaks in psyllium.
3.2. Release dynamics of insulin from drug loaded hydrogels
3.2.1. Release dynamics of insulin from psy-cl-poly(AAm) hydrogels
In present studies, the release profile of insulin from per grams
of the drug loaded hydrogels has been shown in the Fig. 2. The
amount of insulin release in pH 7.4 buffer and distilled water
was higher than the release medium of pH 2.2 buffer. After 24 h
the total amount of drug release, (23.22 ± 2.01) lg, (16.65 ± 1.69)
lg (33.21 ± 1.82) lg per g of gel have been observed, respectively,
in distilled water, pH 2.2 buffer and pH 7.4 buffer. The diffusion
exponent ‘n’ has 0.81, 0.38 and 0.60 values and gel characteristic
constant ‘k’ has 0.87  102, 8.39  102 and 2.73  102 values
in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively.
The values of ‘n’ indicate a non-Fickian diffusion mechanism for
the release of drug in case of pH 7.4 buffer and distilled water. In
this mechanism, the rate of polymer chain relaxation and the rate
of drug diffusion from these hydrogels are comparable. On the
other hand, a Fickian type of diffusion mechanism occurs in case
of pH 2.2 buffer. The values of the initial diffusion coefficients for
the release of insulin were observed to be higher than the values
of average and late time diffusion coefficients in each release med-
ium indicating that in the start, rate of diffusion of drug from the
polymeric matrix was higher (Table 1).
3.2.2. Release dynamics of insulin from psy-cl-poly(AAm-co-MAAm)
hydrogels
The release of insulin, entrapped in a hydrogels, occurs only
after water penetrates the network to swell the polymer and dis-
solve the drug, followed by diffusion along the aqueous pathways
to the surface of the device. In the present studies, the release pro-
file of insulin from per grams of the drug loaded hydrogels has
Diffusion coefficients (cm2/min)
Initial Di  104 Average DA  104 Late time DL  104
18.0 16.95 2.25
7.47 19.88 1.60
19.69 20.44 3.19
8.33 7.61 1.69
5.82 12.75 2.01
7.83 7.96 1.34
 B. Singh, N. Chauhan / International Journal of Diabetes Mellitus 2 (2010) 32–37 35

(a) 100 **psy

95

2121.1
3805.3 3863.4
3754.4

749.3
90

898.3
%Transmittance

1637.7
1560.3
85

3909.4

469.5
1398.2
1269.4
80

1458.2
2926.3

1728.0

1161.3
75

3425.6

1078.3
70

65

60
4000 3000 2000 1000
Wavenumbers (cm-1)

(b) 100 **psyaam

95

897.7
90

85
%Transmittance

2145.7

80

474.5
75 1457.5

70

1042.3
65
2926.1

1664.3

60
3421.6

55

50
4000 3000 2000 1000
Wavenumbers (cm-1)

(c) 95 **AAm MAAm Psy

2366.4

90
85
898.6

80
75
1255.9

70
624.7
%Transmittance

2865.8

65
480.2
1455.4

60
2925.3

1605.5

55
3200.0

50
1095.9

1041.9
3415.6

45
1664.8

40
35
30
25
20
15
10
5
0
4000 3500 3000 2500 2000 1500 1000 500
Wavenumbers (cm-1)

Fig. 1. FTIR of (a) psyllium, (b) Psy-cl-poly(AAm) and (c) Psy-cl-poly(AAm-co-MAAm) hydrogels.

been shown in the Fig. 3. The amount of insulin release in pH 7.4 pH 2.2 buffer. After 24 h total amount of drug release,
buffer and distilled water was higher than the release medium of (52.66 ± 1.29) lg, (28.68 ± 0.88) lg and (53.90 ± 0.77) lg per g of
36 B. Singh, N. Chauhan / International Journal of Diabetes Mellitus 2 (2010) 32–37

Distilled water
Psyllium in the diet also improves glucose tolerance in diabetes
35
pH 2.2 buffer [21,22] This effect may be due to retarded gastric emptying, in-
pH 7.4 buffer
creased intestinal transit or a modification of the secretion and ac-
Amount of drug released (µg/g of gel)

30
tion of digestive enzymes [23]. The human body needs blood
glucose to be maintained in a very narrow range. Insulin and gluc-
25
agons are the hormones which make this happen. It is the produc-
tion of insulin and glucagons by the pancreas which ultimately
20
determines if a patient has diabetes, hypoglycemia, or some other
sugar problem. Psyllium has been proposed as a possible treatment
15
for high blood sugar levels. Studies in humans suggest moderate
reductions in blood sugar levels after a single dose of psyllium,
10
with unclear long-term effects [36]. The brief discussion about
the role of insulin in glucose lowering and in regulating glucose
5
metabolism will be praiseworthy.
People who do not produce the necessary amount of insulin
0
have diabetes. There are two general types of diabetes. Insulin is
30 60 90 120 150 180 210 240 270 300 1440
Time (min.) a hormone that regulates the amount of glucose (sugar) in the
blood and is required for the body to function normally. Insulin
Fig. 2. Release profile of insulin from drug loaded psy-cl-poly(AAm) hydrogels in is produced by cells in the pancreas, called the islets of Langerhans.
different medium at 37 °C.
These cells continuously release a small amount of insulin into the
body, but they release surges of the hormone in response to a rise
60
in the blood glucose level. Without insulin, the blood glucose
Distilled water builds up in the blood and the cells are starved of their energy
pH 2.2 buffer source. The cells will begin to use fat, the energy source stored
pH 7.4 buffer
Amount of drug released (µg/g of gel)

50
40
30
20
10
30 60 90 120
Fig. 3. Release profile of insulin from drug loaded psy-cl-poly(AAm-co-MAAm)
hydrogels in different medium at 37 °C.
gel have been observed, respectively, in distilled water, pH 2.2 buf-
fer and pH 7.4 buffer. The diffusion exponent ‘n’ have 0.60, 0.40 and
0.57 values and gel characteristic constant ‘k’ have 3.29  102,
10.69  102 and 3.46  102 values in distilled water, pH 2.2 buf-
fer and pH 7.4 buffer, respectively. As the values of ‘n’ indicates a
non-Fickian or anomalous diffusion mechanism for the release of
drug in case of pH 7.4 buffer and distilled water. It means that
the rate of polymer chain relaxation and the rate of drug diffusion
from these hydrogels are comparable. On the other hand, Fickian
type of diffusion mechanism occurs in case of pH 2.2 buffer. The
values of the initial diffusion coefficient for the release of insulin
was observed to be higher than the value of average and late time
diffusion coefficient in each release medium indicating that in the
start, rate of diffusion of drug from the polymeric matrix was
higher.
The present drug delivery system will have the double potential
to control the glucose level in the blood. This will release the insu-
lin in the colon in a controlled and sustained manner, and polymer
degradation in the colon will release the psyllium, which itself has
been proposed as a glucose lowering agent. Since the glucose low-
ering effect of psyllium was clearly evident when simultaneously
administered with glucose, the inhibition of glucose absorption
in the gut is a likely contributor to the mechanism of action [20].
for emergencies. When this happens for too long a time, the body
produces ketones, chemicals produced by the liver. Ketones can
poison and kill cells if they build up in the body over an extended
period of time. This can lead to serious illness and coma. In addi-
tion to its role in regulating glucose metabolism, insulin increases
DNA replication and protein synthesis via control of amino acid up-
take, modification of the activity of numerous enzymes, decreased
proteolysis, forces reduction in conversion of fat cell lipid stores
into blood fatty acids, decreased gluconeogenesis, increases amino
acid uptake into cells, forces cells to absorb serum potassium,
forces arterial wall muscle to relax, increasing blood flow, espe-
cially in micro arteries; lack of insulin reduces flow by allowing
these muscles to contract. Although the specific treatments can
150 180 210 240 270 300 1440 vary greatly by subtype of disease, all diabetes treatments have
Time (min.) the same goal; to adequately regulate blood glucose in order to
prevent the primary and secondary effects of hyperglycemia.
Overall the hydrogels can act as double potential drug delivery
systems for the delivery of insulin. These pH responsive hydrogels
can make the site specific delivery of the proteins. Mahkam has
investigated the protective ability of the hydrogel for insulin in
the harsh environment of the stomach, insulin and insulin-incor-
porated polymer-bonded drug by treating with a simulated gastric
solution that contained endopesidase pepsin [37]. The results of
this study indicated that all insulin has been degraded immedi-
ately after contact with gastric fluid. The main cause of degradation
was the proteolytic enzyme, pepsin. After being treated with gas-
tric fluid, all of hydrogels demonstrated a protective effect on insu-
lin and the biological activity remained after the treatment with
gastric fluid of hydrogels [37]. In one case study it is reported by
Wood and coworkers that hydrogels enhances insulin absorption
and holds great promise as an oral insulin delivery system. The
pH-sensitive complexation hydrogels composed of methacrylic
acid and functionalized polyethylene glycol (PEG) tethers, referred
to as P(MAA-g-EG) WGA, can be used for oral protein delivery sys-
tem. The PEG tethers have been functionalized with wheatgerm
agglutinin (WGA), a lectin that can bind to carbohydrates in the
intestinal mucosa, to improve residence time of the carrier and
absorption of the drug at the delivery site. The ability of P(MAA-
g-EG) WGA to improve insulin absorption has been observed in
two different intestinal epithelial models. In Caco-2 cells P(MAA-
g-EG) WGA improved insulin permeability 9-fold as compared
with an insulin only solution, which was similar to the improve-
 B. Singh, N. Chauhan / International Journal of Diabetes Mellitus 2 (2010) 32–37
ment by P(MAA-g-EG). P(MAA-g-EG) and P(MAA-g-EG) WGA have
also been evaluated in a mucus-secreting culture that contained
Caco-2 and HT29–MTX cells. Insulin permeability has been in-
creased 5-fold in the presence of P(MAA-g-EG) and P(MAA-g-EG)
WGA. In addition, it was determined that both P(MAA-g-EG) and
P(MAA-g-EG) WGA were cytocompatible with the Caco-2 and
HT29–MTX cell lines [38].
4. Conclusion
Because of the therapeutic importance of psyllium in curing
diabetes mellitus, hydrogels developing from it can act as double
potential drug delivery devices, indicated from the drug release
dynamics in different release medium. These hydrogels may be
useful for the controlled delivery of peptides. It is concluded from
the drug release dynamics that the drug released through the poly-
meric matrix follows non-Fickian diffusion mechanism pH 7.4 buf-
fer solution, for which the rate of drug diffusion and rate of
polymer chain relaxation are comparable. Therefore, drug release
depends on two simultaneous rate processes, water migration into
the device and drug diffusion through continuously swelling
hydrogels. In each release medium, the earlier stage of the diffu-
sion coefficient has been observed more than the late time diffu-
sion coefficient.
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