-
Iranian Polymer Journal / Volume 8 Number 4 (1999)
1626-1265199
Casein Cross-linked Polyacrylamide Hydrogels : Study ofSwelling
and Drug Release Behaviour
S.K. BajpaiDepartment of Chemistry, Government Science College
(Autonomous), Jabalpur (M .P .), India
'Received 21 June 1995: accepted 5 July 1999
ABSTRACT
The polymeric hydrogels composed of polyacrylamide and food
protein caseinhave been synthesized for the purpose of studying
their swelling and drugrelease behaviour. The two samples,
differing in cross-linking ratio, showalmost Fickian swelling
behaviour (n50 .50) except the less cross-linkedsample at pH 7 .0
for which swelling exponent n was 0 .62, thus showing non-Fickian
swelling behaviour . The swelling parameters like diffusion
exponent,penetration velocity, and diffusion coefficient have also
been evaluated . Theswelling behaviour of hydrogels is greatly
affected by variation in pH of theexternal medium . These gels show
maximum swelling at pH 7 .0 and itdecreases in both acid and
alkaline range . This behaviour has been explainedon the basis of
osmotic swelling pressure theory, thus treating the hydrogel tobe
of ionic nature due to presence of protein casein . The release of
modeldrug bromocresol green (BCG) has been studied as a function of
temperatureof the external medium, and it has been observed that
the amount of drugreleased decreases beyond 40 ' C . The purpose of
undertaking the presentwork is to explore the possibilities of
using casein the natural protein, as adrug delivery device so that
Ike other natural polymers (collagen, guargum,gum arebica etc.)
casein may also be used without causing any toxic effect inthe
human body system. These gels also undergo a number of
reversibleswelling-deswelling cycles.
Key Words: hydrogels, equilibrium swelling capacity,
cross-linking, casein, polyacrylamide
INTRODUCTION
researchers and technologists due to their
widespreadapplications in contact lenses [i], wound dressings
Hydrogels are water-swellable, three-dimensional
[2], drug delivery systems [3, 4], controlled release
ofpolymeric networks possessing both the cohesive
perfumes [5], adsorption of proteins [6] and metalproperties of
solids and diffusive transport properties
ions [7] etc.of liquid. They have been increasingly attracted
to
However, most of the research work on
231
-
Casein Gyms-linked Pnlyaerylamide Hydrogels : Study a(Swelling
and Aug Release
polymer gels is mainly focused on five syntheticpolymeric gels,
thus neglecting the considerablevariety of networks in natural
polymers such asnaturally occurring polysaccharides, proteins
etc.Since the biological responses to polymer surfaces arecomplex,
each polymer system should meet certainrequirements for biomedical
applications.
Biocompatibility of the material is critical, andfor some
applications biodegradability is desirable.The natural gels are
ideal candidates for thesebiomedical applications . For example,
they could beused to encapsulate the cultivate cells inside the
gel,where the network will act as a semipermeablemembrane allowing
only growth factors to enter to aidthe growth of the cells . The
study of gels could beuseful in the development of novel synthetic
polymernetworks that mimic natural gels [8], and a knowledgeof the
response of natural gels to the changes in theenvironment could be
invaluable varifying the trendsobserved in the experimental
behaviour of syntheticpolymeric gels.
In recent past the researchers have focused theirattention on
studies related with synthesis, swellingbehaviour and drug release
analysis of naturallyoccurring polymeric hydrogels in the form
ofnanoparticles, thin films, microspheres etc. Forexample, collagen
[9], chitosan [10] guar gum [I1],agarose [12], gum arabica [13]
have been successfully
Table 1 . Raw materials employed and their source.
CaseNo .
Name and description_
Source
1 Acrylamide (Mm) Robert Johnson '
2kW- Methylene bisacrylamide Central Drug(131S) House'
3 Casein powderLoba Chemie
4 Potassium persulphate (KPS)
Industries'Loba Chemie
5 Sodium metabisulphite (MSS)IndustriesS .D. FineChemicals '
6 Bromocresol green (BCG) Central DrugHousea . India
used as drug delivery devices for anticancer drugs,antibiotic
drugs, colonic drugs, antimicrobial drugs,protein and peptide drug
delivery respectively. In thisconnection, the author has already
reported theswelling behaviour of hemoglobin
cross-linkedpolyacrylamide hydrogels [14] and in continuation
thepresent communication describes the analysis ofswelling
behaviour of casein cross-linkedpolyacrylamide hydrogels . The
equilibrium swellinghas been studied as a function of pH of the
externalsolution . The model drug release behaviour ofhydrogels has
also been analyzed.
EXPERIMENTAL
MaterialsThe raw materials used have been described in TableI.
Acrylamide was recrystallized in methanol before
use and other material were used as received . Thedoubly
distilled water was used throughout the work.
Synthesis of Cross-linked HydrogelsA definite amount of casein
powder was dissolved inNaOH solution and then acrylamide (AAm) and
N,N'-methylene bisacrylamide (BIS) were added in definiteamounts
and mixed thoroughly, followed by additionof calculated quantities
of potassium persulphate(KPS) and sodium metabisulphite (SMB) . The
totalmixture was stirred well quickly to avoid lumping,poured into
10 x 75 mm test tubes and set asideundisturbed. The resulting
smooth, semi-transparentcylindrical hydrogels were removed from the
testtubes and then sliced into discs, washed with Tris-HCIbuffer,
pH 7.0, followed by acetone and water anddried, in a dust free
glass chamber at roomtemperature . In all, two samples of hydrogels
wereprepared with different cross-linking ratio X(X = molBISlmol
AAm). These samples will be denoted asCas-PAAm X (2 .1) and
Cas-PAAm X (1 .7) wherenumber in the parentheses represent the
cross-linkingratio in mol % (Table 2). Scheme I describes
theformation of hydrogel in systematic way. In order toprepare the
drug loaded gel, the calculated amount ofmodel drug bromocresol
green (BCG) was added to
232
Iranian Polymer Journal /Volume 8 Number 4 (1999)
-
Bajpai 5-K.
Casein
solution ofcasein
hydrogels . After the attainment of equilibrium theswelling
capacity was calculated using the formula:
Grams of water per gram of gel = W W ( 1 )
Where W, is the weight of the equilibrated hydrogeland W is the
initial weight of the dry hydrogel.
The penetration velocity (V) of buffer in eachpolymer was
determined by weight gain method asreported elsewhere [15] . The
penetration velocity wascalculated from the slope of the initial
portion of thepenetrant uptake curve by using the equation:
1 dWgV =
2dA dt
dissolution in NaOH
:7.=ga.=:==ittsm
SMB + KPS AAm + BIS(2)
cross-linkedhydrogel
where V denotes penetration velocity, dW,/dt denotesthe slope of
the weight gain versus time curve, ddenotes the density of water at
37 'C, and A denotesarea of one face of the disc.
The mass uptake of the swelling solution M, asa function of time
t was analyzed according to the eqn(3) [16],
Schematic diagram showing the formation of
Cas-PAAmXhydrogels.
M _ kt aM,, (3)
Scheme I
the reaction mixture before adding sodiummetabisulphite and
potassium persulphate
. There is noparticular reason for selecting bromocresol green
as amodel drug because the purpose of study is just tohave an
understanding about the drug releasingcapacity of the proposed
hydrogel, so that it could beused as a model drug-releasing device
in near future.The semi-transparent greenish hydrogel discs
wereobtained.
Dynamic Swelling StudiesHydrogels were swollen to equilibrium in
water atphysiological temperature 37 'C . Equilibrium wasattained
in 20 h, and the approach to equilibrium wasmonitored by
measurement of mass of the swollen
Eqn (3) could be used to find out the Fickianand non-Fickian
absorption of water by hydrogel.is the mass uptake of the solvent
at equilibrium, k is aconstant and n is the exponent describing the
Fickianor anomalous swelling mechanism.
On taking natural log of eqn (3):
InM =Ink+nlntM m
The values of n and k were calculated from theslope and
intercept of the plot of In against In t,respectively.
The diffusion coefficient D of solvent wascalculated using the
following equation [I7]:
0 = k(nr 2 ) a4
(5)
(4)
233Iranian Polymer Journal / Volume 8 Number 4 (1999)
-
Casein Cron-IiWcM Polyacrylamide Hydrogen :: Study of Swelling
and Drug Release
Table 2 . Composition of Cas-PAAm hydrogels.
SI . System Composition (g)No . Cas AAm BIS BCG SMB KPS H2O
1 Cas-PAAmX(2.1) 4 .0 4 .0 0.19 0.00 0 .10 0 .10 402 Cas-PAAmX(1
.7) 3 .0 5 .0 0,19 0.00 0 .13 0 .13 403 Cas-PAAmX(2.1) 4 .0 4 .0
0.19 0.02 0 .10 0 .10 404 Cas PAAmX(1 .7)
(Drug loaded) 3 .0 5 .0 0.19 0.02 0 .13 0 .13 40
where, r is the radius of the gel disc.To study the swelling
behaviour of the
hydrogels in medium of different pH, two pieces ofpreweighed
hydrogels were placed in buffer solutionof required pH and allowed
to equilibrate . Massmeasurements of the hydrogels were taken at
differenttime intervals to monitor the attainment ofequilibrium,
and swelling capacities (water sorbed perg of gel) were determined.
In each case the final watercontent was determined for two pieces
of hydrogels.Good agreement was found in the degree of swellingfor
both pieces, each having the same history, theaverage of two
determinations being used forcalculations.
In order to study the reversibility of theswelling process, the
hydrogel samples were allowedto equilibrate in water and then
placed in 2 M NaClsolution, which caused the gel to deswell .
Thedeswelling was then followed by weighing the gel atvarious time
intervals. The reversibility of swellingand deswelling was
determined using the samesamples for consecutive swelling and
deswellingexperiments . The degree of swelling has beenexpressed as
the swelling ratio, the ratio of finalweight of the gel to initial
weight of the gel.
In another set of experiments, completely driedhydrogel was
allowed to equilibrate in water and afterattainment of the
equilibrium it was dried again . Thedried hydrogel, was further
allowed to swell in water,and then this process of drying and
swelling wasrepeated a number of times.
In order to study the drug release analysis, thedrug-loaded
hydrogels were placed in externalmedium at pH 7 .0 and the
absorbance of the solutionwas measured (Systronix, India) at
definite time
intervals. The amount of active ingradient released M,at a time
t was determined using Beer-Lambert law.The total amount of drug
incorporated in the disc wastaken as M,,.
RESULTS AND DISCUSSION
Dynamic Swelling StudiesA critical analysis of the swelling
process reveals thatthere are two underlying molecular
processes:penetration of the solvent molecules into the voidspaces
in the network and subsequent stretching orrelaxation of the
network segments . The fundamentalequation M,/M.,,=kt" defines the
following threesituations:For a perfectly Fickian process where the
rate ofsolvent penetration is the slowest and hence is the
ratelimiting step, the value of n=0 .50.When the penetration
velocity is far greater than thechain relaxation rate, the solvent
uptake isproportional to time, i .e., n= 1 .0 (This is often
calledrelaxation-controlled case-lll transport) [18].When both the
diffusion and polymer relaxationcontrol the overall rate of water
uptake, the diffusionmechanism is non-Fickian i .e ., 0 .5
-
5epai S .K.
Table 3. Swelling parameters of Cas-PAArnX hydrogels at
different pH over a period of 20 h with a temperature=37 'C.
pH System Equilibrium swelling capacity Penetration velocity n k
Diffusion coefficientH20 :gel (gig) V x 105 (curls) DK105 (cm2ls)2
.0 Cas-PAAmX(2 .1) 1 .10 0.98 0.11 0.18 1 .78
Cas-PAAmX(1 .7) 1 .86 1 .67 0.20 0.28 2 .864 .0 Cas-PAAmX(2 .1)
3.61 2.17 0.32 0.27 3 .04
Cas-PAAmX(1 .7) 4.92 3.06 0.42 0.40 4 .267 .0 Cas-PAAmX(2 .1)
6.19 5.02 0.56 0.41 4 .29
Cas-PAAmX(1 .7) 7.82 6.08 0.61 0.57 6.819 .0 Cas-PAAmX(2 .1)
5.20 3.15 0.49 0.38 4.01
Cas-PAAmX(1 .7) 6.15 4.87 0.55 0.47 5.01
thus following transport mechanism with a chainrelaxation
contribution.
Effect of pHThe swelling behaviour of hydrogels is
greatlyaffected by variation in pH of the external solution
asdepicted in Figure I . The results so obtained are quitedifferent
from those obtained in the case of gelatin-swelling was found to
decrease with increase in pH of
9 .0D Cas-PAArnX (1 .7)
r r 1 r2 .0
4 .0
6 .0
8 .0
10.0pH
Figure 1 . Effect of pH on the equilibrium swelling
capacity;temperature = 37 ' C .
polyacrylamide hydrogels [19], where the equilibriumthe external
solution . It is clear from the Figure I thatthe equilibrium
swelling capacity increases with risein pH of the external
solution, attains maximum valueat pH 7 .0, and then starts
decreasing, as the pH goes inthe alkaline range. It is also clear
from the figure thatswelling is suppressed to a greater extent in
the acidicrange as compared to the alkaline one.
In order to explain the observed experimentalfindings, two
possible theories may be proposed. Firsttheory is based on the
formation of a complexstructure in the polymer matrix through
H-bondinginteractions between -COOH and -CONH2 groupsdue to
hydrolysis of amide groups of polyacrylamidein the polymer matrix
[20]
. This theory clearly impliesthat the variation in swelling
behaviour of Cas-PAmXhydrogels must be due to possible hydrolysis
ofpolyacrylamide and hence it should play a key role ingoverning pH
dependent swelling behaviour.
Now, in order to verify the above theory,hydrogels of
polyacrylamide, with the same cross-linking ratio, were prepared in
absence of othercomponent casein . When these gels were put
invarious buffer solutions of different pH, the swellingwas found
to be almost the same for all pH values . Ifthe above proposed
theory were correct then thehydrogels of cross-linked
polyacrylamide should haveshown the similar pH dependent behaviour
asobserved with Cas-PAAmX hydrogels . This clearlyverifies that no
such complex structure formationtakes place within the polymer
matrix and obviouslypolyacrylamide does not play any role in
governingthe observed pH - effect. Therefore it must be the
7 .0
5.0
3 .0
1.0
Iranian Polymer Journal / Volume 8 Number 4 (1999)
235
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Casein Cross.linked Polyasrylamidc Hydrogen : Study of Swelling
and Drug Rana.
other component of polymer matrix, namely casein,which should
play the key role in the explanation ofobserved behaviour.
After failure of the above theory we nowproceed for the other
theory, according to which theswelling behaviour of ionic hydrogels
in diluteelectrolyte solution is mainly due to osmotic
swellingpressure between the gel phase and external solution.At the
moment, the above theory seems to be quite fitfor the present study
because casein, one of thecomponents of the hydrogel, is a
polyelectrolytecontaining charged and dissociable groups along
themacromolecular chain.
The kinetic swelling behaviour of an ionichydrogel depends upon
mass transfer limitations,Donnan equilibrium considerations, ion
exchange andionic interactions [21] . When such an ionic hydrogelis
immersed in a high dielectric constant medium,these ionic moieties
will dissociate and create anoverall charge density along the
chains, as well as ahigh concentration of mobile ions in the gel .
Ascompared to the non-ionic gel behaviour, this ioniccharacter will
introduce two "new player" forces inthe system: the osmotic
pressure resulting fromdifference in ion concentrations between the
swollengel and the external solution i .e., Ir is ,
(for"macroscopic" electroneutrality reasons, mobile ionsbelonging
to the gel can not leave it and henceminimization of this osmotic
pressure can only beachieved through dilution of the network
chargedensity i .e ., swelling) and the net charge density alongthe
chains will generate some electrostatic repulsion(i.e ., coulombic
forces) between chain segments rze 1,.The resulting expansion of
the network will contributeto the overall swelling behaviour [22] .
It has beenshown by theoretical calculations and
experimentalresults that
is typically similar than nia,.For a weakly charged polymer
network in a
dilute electrolytic solution, the osmotic swellingpressure
is given as:
a 1e = RTE(C8 C;)
(6)
where Cg and C, are the molar concentrations ofcounter ions in
the gel and solution phase
respectively, R is general gas constant and T is theabsolute
temperature.
K-casein is an amphiphilic protein which hastwo identifiable
regions : amino acids 1105containing predominantly hydrophobic
residues and106169 containing hydrophilic charged amino
acidresidues . It is the latter portion that contributestowards the
hydrophilic nature of casein . In addition,oligosaccharide chains
consisting of sialic acid,galactose and N-acetylgalactosamine are
grafted ontothreonine at positions 131 and 135 in the amino
acidsequence. This also contributes to the hydrophilicityof this
portion of K-casein.
Since the synthesis of hydrogel involves thedissolution of
casein in 0.1 N NaOH, the hydrogelcontains undiffusable COO- groups
along themacromolecular chain and a high concentration ofmobile
counter ions in the gel phase . When thishydrogel is placed in the
doubly distilled water at pH7.0, obviously the difference Cg Ca
becomes verylarge, thus resulting in a high osmotic
swellingpressure nie,,, and ultimately high degree of swelling.The
mutual repulsion of 000- groups along themacromolecular chain also
promotes the swelling.
When the hydrogel is placed in the buffersolution of pH 4.0, the
dissociation of COOH groupspresent along the macromolecular chain
is suppressedand hence concentration of counter ions inside the
gelphase i.e ., Cg decreases and hence Ce C, becomescomparatively
small . Moreover, since the pH ofexternal solution is just below
the isoelectric pH of thecasein (i .e ., 4 .6), NH2 groups present
along thecasein molecules also get protonated to a little extent.In
this way the mutual attraction between the twooppositely charges
groups NH ; and 000- alsocauses the polymer segments to contract
(n, ) . Bothof these factors cause a decrease in the degree
ofswelling.
In the case of pH 2 .0 of external solution thedissociation of
COOH groups is suppressed to such agreat extent that the difference
C i Ci becomesextremely small . Therefore minimum swelling
isobserved . Here it is worth mentioning that theswelling observed
at this pH is mainly due to theelectrostatic repulsion between the
similarly charge
236
Iranian Polymer Journal / Volume 8 Number 4 (1999)
-
Bgpri S.K.
NH; groups along the segment. Moreover some
contribution of hydrophilic tendency of polyacryl-amide should
also be taken into account.
In the alkaline range although the dissociationofCOOH is
complete, thus providing a large numberof counter ions in the gel
phase but at the same timethere exists a higher concentration of
Na+ and OWions in the external solution
. As a result the differenceCg C, becomes small thus resulting
in decrease inosmotic swelling pressure as well as extent
ofswelling
. However the suppression in the degree ofswelling in alkaline
medium is not to such a greatextent as found in the acidic medium.
This may becontributed to the fact that in alkaline medium
themutual repulsion among COO
- groups is morepredominant . The values of swelling exponent n
atdifferent pH of the external solution (Table 3) alsosupport the
proposed mechanism.
Reversibility of Hydrogel SwellingThe ability of hydrogel to
undergo several cycles ofswelling and deswelling is shown in Figure
2
.,6. It canbe seen from Figure 2a that after the first cycle the
geldid not achieve its original swollen state and in all
thefollowing cycles it swelled back to its previousswollen
state
. Since the virgin gel was used withoutany prior washing, some
salt might have been presentwhich could have leached out upon
deswelling, thusreducing the degree of successive swelling.
When the freshly prepared gel is placed in thedoubly distilled
water at pH 7
.0, the swelling occursto maximum in accordance with the
Donnan-membrane equilibrium
. Now when this swollen gel isplaced in 2 M NaCl solution, the
concentration ofosmotically active ions in the external
solutionbecomes high and hence this results into diffusion ofwater
molecules from gel phase into outer solution,thus causing the gel
to deswell
. Due to reversibilityand rapidity of swelling, the gel could be
consideredas a mechanochemcial system in which chemicalionization
energy could be transformed directly intomechanical energy
[23].
It is also clear form the Figure 2b that whencompletely dried
gel is placed in water it attainsalmost maximum swelling in every
cycle
. This shows
0 .010 SI DS1 S2 DS2 S3DS3 S4 DS4
Cycles
(a)
8 .0
6.0
0
2 .0
0.0 .Di Si D2 S2 D3
Cycles(b)
Figure 2 . (a) : Reversibility of swelling, of Cas-PAAmX(l
.7)hydrogels ; pH=7.0 ; temperature=37 'C ; 10 indicates
initialcondition ; Si=swelling cycle equilibrium condition and
DSi=deswelling cycle equilibrium condition . (b) :
Reversibleswelling and drying of Cas-PAmX(I .7) hydrogels,
pH=7.0;temperature=37 'C ; Di=dried state; Si=swollen state of
gel.
that during the swelling process the gel does notundergo any
irreversible structural change and hence
8 .0
2 .0
Iranian Polymer Journal / Volume 8 Number 4 (1999)
237
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Casein Crosslinked Nolyacrylamide Hydrogels : Study of Swelling
and Drag Rckase
it swells back to maximum when placed in water.During swelling,
the shape of the gel sample
followed a repeatable pattern. Initially a swelling front
moved inward separating the swollen surface layerand the
unswollen inside core
. As a result, the sampleassumed a dumbbell shape
. Observation through anoptical microscope showed the presence
of stresses.The surface of the gel was full of cracks
whichdisappeared after a while, yet the dumbbell shape
wasmaintained, although it gradually changed back tocylindrical
shape . This behaviour was observed duringthe swelling of all
samples including dried samples.Similar observations were reported
by Tanaka et al.1241 as mechanical instabilities during the
swelling ofpolyacrylamide gel beads
. It is concluded that the thinswollen layer would be in
mechanical constraint dueto the free outer surface and fixed inner
surface.Hence two opposing forces, one forcing the gel toswell and
the other to remain unswollen would beresolved depending upon the
osmotic pressuredeveloped.
Drug Release AnalysisThe model drug release behaviour of
Cas-PAAmXhydrogels has been studied " as a function oftemperature
of the external medium. When the drugloaded hydrogel is placed in
the double distilled waterat pH 7 .0 at 37 'C, water diffuses into
the polymermatrix owing to the swelling osmotic pressure .
Thepenetrant molecules diffuse into the gel and displacethe drug
particles which ultimately diffuses out of thedevice due to
increased chain relaxation. It wasobserved that initial rate of
drug release was higherwhich may be contributed to the fact that
when gel isplaced in solvent, the outermost surface of thepolymer
matrix immediately comes in contact with itand the solvent diffuses
into the gel phase, followedby release of drug
. Similar observations have alsobeen reported elsewhere
[25].
Figure 3 describes the effect of temperature ondrug releasing
capacity of drug loaded hydrogel withthe cross-linking ratio 2.1
and 1 .7 mol % . Here theamount of drug released in a period of 20
h has beenplotted against the temperature of the externalsolution .
It is clear from the figure that there is an
q Cam-PAAmX (1 .7)90
10
10
20
30
40
50
50Temperature (C)
Figure 3 . Amount of drug released in a period of 20 h as
afunction of temperature of the external solution pH = 7
.0.
increase in the amount of drug delivered up to 40 'C,and then it
decreases . Initially the observed decreasein the amount of drug
released beyond 40 -C wasthought to be due to formation of some
complexstructure between the amide groups and carboxylicgroups,
which were produced due to possiblehydrolysis of polyacrylamide .
However, when thesame experiment was conducted with the drug
loadedhydrogel of cross-linked polyacrylamide alone, thetheory
proved to be wrong, as there was no decreasein the amount of drug
released beyond 40 *C. Thisclearly showed that no such complex
structure formedinside the polymer matrix . In fact, an increase
intemperature from 25 to 40 ' C shows a higher andfaster drug
release due to the extensive swelling andchain relaxation
. An increase in temperature beyond40 'C shows a decrease in
drug release due to decreasein solubility of casein.
Effect of Cross-linkingThe degree of cross-linking of a hydrogel
networkplays a significant role in controlling its
swellingbehaviour. In the present study, two hydrogel sampleswith
the cross-linking ratio in mol % 2
.1 and 1 .7 havebeen used, of which sample Cas-PAAmX (1
.7)showed a greater swelling tendency than the other one(Figure
I)
. This behaviour of hydrogels is very
70
30
238
Iranian Polymer Journal / Volume 8 Number 4 (1999)
-
Baja. s .ic.
common and may be attributed to the fact that byincreasing molar
percent of cross-linker to monomer(i .e ., lightly to highly
cross-linked) the number ofefficient cross-links per unit volume
increases withthe result that there is less free volume or
roomavailable to accommodate solvent, and hence degreeof swelling
decreases.
CONCLUSION
The swelling behaviour of casein cross-linkedpolyacrylamide
hydrogels has been found to be pH-dependent and it favours the
medium with neutral pH7 .0 . This effect could be explained well on
the basis ofosmotic swelling pressure theory. These gels
alsoundergo a number of reversible swelling-deswellingcycles while
maintaining their structural integrity . ThepH-dependent and
reversible swelling behaviourcould be very useful in the
development of artificialmuscle or physiologically sensitive drug
deliverysystems and extraction of biocomponents from
dilutesolutions by a modified gel filtration technique.
The drug loaded gels release the drug over aperiod of 24 h and
hence there is some possibility ofusing these gels in the case of
short term drug deliveryapplications where an immediate or fast
relief isneeded. The non-toxic nature of casein is also afavourable
factor for its possible use as drug deliverydevice. In brief, the
aim of the proposed study to lookfor the possibilities of using
casein as a material fordrug delivery devices has been achieved to
someextent.
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