ISSN: 0975 -8542

Journal of Global Pharma Technology

Available Online at www.jgpt.co.in

RESEARCH ARTICLE

Synthesis of a New Three-Dimensional Network Co-polymer and

Studying the Ability of Drug Delivery System
Zahraa Mushtaq Abd Al-Aama & Mohammad N. AL-Baiati*

Department of Chemistry/ College of Education for Pure Sciences/University of Karbala

Holy Kerbala/ Iraq.

*Corresponding Author: dr.baiati@gmail.com

U U

Abstract

In this work, a new co- polymer was synthesized from the reaction of pentarythritol with fumaric acid to
form the linear co- polymer. Three different moles of acrylic acid monomer (0.5, 1.0 and 1.5 mole), were
added to obtain three new co- polymers. Swellingof the polymer samples were measured in the buffer
solution in the basic and acidic medium. The albumin protein was loaded onto the co- polymer samples
and then the release of the albumin protein was measured in the acid and basic medium.The results
obtained showed that the protein loading and release process in the basic medium were higher than in
the acidic medium, indicating that the combined co-polymer is selective in the medium.

Keywords: Hydro gel; Polymer; Condensation polymerization; Three-dimensional network; Selectivity;

Swelling; Buffer solution; Drag delivery system.
Introduction
Hydro gel is three-dimensional, hydrophilic, properties of hydro gels have stimulated
polymeric networks capable of absorbing particular interest in their use indrug
amounts of water or biological fluids[1]. Due delivery applications[8]. Their highly porous
to their high water content, porosity and soft structure can easily be tuned by controlling
large consistency, they closely simulate the density of cross-links in the gel matrix
natural living tissue, more than any other and the affinity of the hydrogels for the
class of synthetic bio-materials [2]. Hydro gels aqueous the environment in which they are
may be chemically stable or they may degrade swollen [9].
and eventually disintegrate and dissolve [3].
Their porosity also permits loading of drugs
They are prepared from materials such as into the gel matrix and subsequent drug
gelatin, polysaccharides, cross-linked poly acr release at dependent on the diffusion coefficie
yl amide polymers, polyelectrolyte complexes, nt of a small molecule or a macro- molecule
and polymers or copolymers derived from through the gel network [10]. Since the
methacrylate esters[4]. They are insoluble in polymer cannot dissolve due to the covalent
water and are available in dry or hydrated cross-links, water uptakes far in excess
sheets or as a hydrated gelin drug delivery ofthose achievable with hydrophilic linear
systems designed for single use [5]. Further- polymers can be obtained [11]. Indeed, the
more, hydrogels can be formulated in a benefits of hydrogels for drug delivery may be
variety of physical forms, including largely pharmacokinetic-specific ally that a
slabs,micro particles, nanoparticles, coatings, depot formulation is created from which
and films[6]. As a result, hydro gels are drugs elute slowly; maintaining a high local
commonly usedin clinical practice and concentration of drug in the surrounding
medicine with a wide range of applications, tissues over an extended period of time,
including Tissue Engineering and although can also be used for systemic
Regenerative Medicine; Diagnostics, Cellular delivery [12]. Hydrogels are also generally
immobilization, Separation of bimolecular or highly biocompatible, which may be attrib-
cells, and barrier materials to regulate uted to the high water content of hydrogel
biological adhesions [7].These unique physical .Biodegradability or dissolution in case of

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 Zahraa Mushtaq Abd Al-Aama et. al.: Journal of Global Pharmacy Technology. 2017; 12(9):50-56

hydrogels may be broughtaboutby enzymatic, stirrer, and using Methylethylketone peroxide

hydrolytic, or environmental (e.g. pH, (MEKP), as a hardener (initiator cross-linking
temperature, or electric field) pathways; process), and cobalt octet 6% (as a
however, degradation is not always desirable accelerator). Three different co-polymers were
depending on the time frame and location formed, different between them from where
ofthe drug delivery device[13].Hydrogels, number of moles of the acrylic acid monomer
with high water content as well as tissue like adds to it. After preparation the samples of
mechanical properties,have been polymeric molded in matrixes glasses, where
demonstrated to be capable of combining with hardened resins and measurements
cells to engineer various tissuesin both vitro (110x50x30) and cutting as a disc in
and vivo [14, 15]. dimensions (thickness=3.0 mm and
diameter=1.0 cm) according to ASTM: D-
Experimental
2849[15]and the weighted of the xerogel discs
All chemicals used were produced by was exactly 0.4 gm of all samples were used in
companies (B.D.H), (SIGMN), (C.D.H) and the swelling study.
(MERCK).
Preparation of Standard Calibration
Preparation of Modified Co-polymer Curve[16]
In a 250 ml three-necked round bottom flask, A standard curve for albumin was determined
(4.0 mole, 464 gm) of Fumaric acid, and (1.0 by preparation solutions different
mole,136 gm) of Pentaerythritol, were mixed concentrations from albumin in the range of
together, this flask was equipped with a (0.025- 0.25 %). The solutions were prepared,
thermometer and a mechanical stirrer. The usingdemonized water as solvent. The
mixture warmed carefully with an electric absorbance of the resulting solutions was
heating mantel to 140Cᵒ until a clear liquor is measured at λmax 398.0 nm using demonized
formed and then about 15 ml of Xylene was water as a blank.Figure (3) showed the linear
added carefully to the reaction flask, in the relationship between the concentration of the
form of batch (two drops in each batch), albumin and the absorbance.
withdrawal of water formed in the Drug (Albumin) Loaded
esterfication process, and the flask was gently
heated. Heating was stopped after 60 min. The albumin is a family of globular proteins, is
at180Cᵒ, until no more water came off. The water-soluble, and moderately soluble in
flask was allowed to cool to 50Cᵒ, and (1.36x10- concentrated salt solutions, experience heat
3 mole, 0.147 gm)of Hydroquinone was added denaturation, and because the prepared gels
to the reaction flask, with stirred by are swell extensively in water[17], the
mechanical stirrer. The negative test of albumin was loaded through immersing the
NaHCO3 solution proves that the prepared xerogel discs in buffer solution pH (pH=2.2
modified polyester resin doesn't contain un- and pH=8.0) containing different weights of
reacted acid. albumin and was allowed to loaded for each
hour at constant temperature (310 K). After
Equation (1), represents the preparation of the every 1hr., they were removed from the buffer
modified co-polymer; and at 55Co about (0.5, solution, blotted with filter paper to remove
1.0 and 1.5 mole) which equal (36,72 and 108 surface water, weighted and the albumin
gm), respectively of Acrylic acid monomer, was content ratio was calculated by using
added to the modified co-polymer and stirred Equation (2)[18]; and the same time the
by mechanical stirrer, untila pourable syrup absorbance of the albumin concentration in
was formed. Table (1), represents the physical buffer solutions was evaluated by using UV.-
properties of modified co-polymer. Figure (1) spectrophotometer. The measurement was
represent the FT-IR spectrophotometer of continued until a constant of disc content was
prepared co-polymer and Figure (2) represents repeated for each sample.
the 1HNMR spectrophotometer of prepared co- Drug (Albumin)Release
polymer.
A loaded hydrogel disc is used in order to
Preparation of Polymeric Specimens determine the amount of albumin released
The samples of polymeric prepared by add from the hydrogel network. After reaching the
different number of moles of the acrylic acid equilibrium state of the disc from through a
monomer (0.5, 1.0and 1.5mole) to the modified constant of disc content in a buffer solution
resin prepared in step above with continuous marinated in it. Loaded hydro gel disc

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 Zahraa Mushtaq Abd Al-Aama et. al.: Journal of Global Pharmacy Technology. 2017; 12(9):50-56

immersed in 50 ml deionizer water at ethylene in the structure of polymer, the

temperature (310 K). The amount of albumin multiples at 4.24- 4.50 ppm of methyl
release was evaluated each hour.The protons, but the triplet signal in 3.44- 3.62
measurement of release was continued until a ppm due to the proton of aliphatic alcohol, so
stability absorbance was repeated for each this spectrum was confirmed the structure of
sample. our target polymer.
Results and Discussion Drug (Albumin)Loaded
Preparation of Co-polymer A plot of albumin content (%) versus time
showed the curves of modified resin for three
Figure(1), showed the appearance of a strong
different numbers of moles from acrylic acid
broad band at about 3338cm-1 for stretching
compositions ranging from 0.5, 1.0 and 1.5
carboxylic acid (-OH) with stretching (H-
mole, against loaded time (hour) at constant
bond), and also showed a weak band at about
temperature (310 K) , as shown in Tables (2)
2953 cm-1 due to the =C-H for carboxylic
to (4), respectively for pH= 8.0 and as shown
acid, and the spectrum also showed a weak
in Tables (5) to (7), respectively for pH=2.2, by
band at about 2887 cm-1 due to C-H
using UV-Spectrophotometer and measuring
aliphatic, and the spectrum also showed a
the absorbance of the solutions.
strong band at about 1718cm-1 assigned to a
stretching band C=O for ester group and also Release of Drug (Albumin)
showed a bands at about 1014 cm-1 assigned Tables (8) to (10), represent the release of
to C-O absorption band. Figure(2), showed albumin from the measured samples in the
the spectrum of 1HNMR, which explain the basic medium pH=8.0. Tables (11) to (13),
singlet signal, at 13.24 ppm characteristic of represent albumin release from measured
proton in carboxylic acid group furthermore models in the acidic medium pH=2.2.
the multiples in the region 7.53- 8.10 ppm
back to all protons in aromatic ring, the
signals at 6.27-6. 46 ppm for four protons of

Equation 1: Preparation of the modified co-polymer

Table 1: Physical properties of the modified resins after addition of acrylic acid monomer
Physical properties Value
Around 1840 gm/mole
Molecular Weight ( Mn ) 57 %
Solid content 21 poise
Viscosity 12-16 min at 25C0
Gel time 26
Acid Value 1.3 (gm/cm3 )
Density

Figure 1: The FT-IR spectrophotometer of the prepared co-polymer

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 Zahraa Mushtaq Abd Al-Aama et. al.: Journal of Global Pharmacy Technology. 2017; 12(9):50-56

Figure 2: The 1HNMR spectrophotometer of the prepared co-polymer

Figure 3: Calibration curve of the albumin (the absorbance in 1cm cell) at λ max 398.0 nm

(Wt. of hydrogel-wt. of xerogel )

Swelling ratio (%) = ------------------------------------------ x100 ….. equation (2)
(Wt. of hydrogel)

Table 2: Albumin content (%) and absorption of solution (Abs.) per hour, of modified resin containing 0.5 mole of
acrylic acid monomer at pH=8.0, Temp.=310K
Time Concentration of albumin
(hour) 0.025 0.075 0.125 0.175 0.225
% Abs. % Abs. % Abs. % Abs. % Abs.

1 9.77 0.444 11.99 0.488 13.98 0.528 15.97 0.569 17.42 0.601

2 11.78 0.425 13.90 0.466 15.88 0.509 17.98 0.548 19.63 0.580

3 13.46 0.408 15.56 0.449 17.71 0.488 19.98 0.529 21.80 0.561

4 15.29 0.388 17.27 0.429 19.31 0.471 21.55 0.509 23.88 0.541

5 15.29 0.373 17.27 0.414 19.31 0.460 21.55 0.499 25.48 0.521

Table 3: Albumin content (%) and absorption of solution (Abs.) per hour, of modified resin containing 1.0 mole of
acrylic acid monomer at pH=8.0, Temp.=310K
Time Concentration of albumin
(hour) 0.025 0.075 0.125 0.175 0.225
% Abs. % Abs. % Abs. % Abs. % Abs.

1 10.43 0.444 13.02 0.477 15.68 0.518 17.98 0.559 19.45 0.592
2 12.82 0.425 15.16 0.458 17.61 0.499 19.98 0.538 21.55 0.571

3 14.68 0.408 17.24 0.439 19.63 0.478 21.91 0.519 23.72 0.550

4 16.58 0.388 19.21 0.419 21.55 0.458 23.55 0.499 25.91 0.531

5 16.58 0.373 19.21 0.409 21.55 0.449 23.55 0.489 27.26 0.511

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 Zahraa Mushtaq Abd Al-Aama et. al.: Journal of Global Pharmacy Technology. 2017; 12(9):50-56

Table 4: Albumin content (%) and absorption of solution (Abs.) per hour, of modified resin containing 1.5 mole of
acrylic acid monomer at pH=8.0, Temp.=310K
Time Concentration of albumin
( hour) 0.025 0.075 0.125 0.175 0.225
% Abs. % Abs. % Abs. % Abs. % Abs.
1 12.40 0.411 15.00 0.457 17.04 0.499 19.45 0.536 21.61 0.571

2 14.48 0.395 17.13 0.438 19.27 0.477 21.38 0.519 23.56 0.551

3 16.27 0.373 19.09 0.419 21.10 0.459 23.43 0.499 25.76 0.531

4 18.22 0.355 21.03 0.399 23.06 0.439 25.46 0.479 27.85 0.512

5 18.22 0.344 21.03 0.388 23.06 0.429 25.46 0.469 29.92 0.491

Table 5: Albumin content (%) and absorption of solution (Abs.) per hour, of modified resin containing 0.5 mole of
acrylic acid monomer at pH=2.2, Temp. =310K
Time Concentration of albumin
(hour) 0.025 0.075 0.125 0.175 0.225
% Abs. % Abs. % Abs. % Abs. % Abs.
1 5.10 0.500 7.06 0.549 9.20 0.589 11.45 0.629 13.66 0.660

2 7.41 0.488 9.32 0.528 11.50 0.569 13.05 0.609 15.29 0.641

3 7.41 0.470 9.32 0.519 11.50 0.559 13.05 0.599 17.64 0.622

Table 6: Albumin content (%) and absorption of solution (Abs.) per hour, of modified resin containing 1mole of acrylic
acid monomer at pH=2.2, Temp. =310K
Time Concentration of albumin
(hour) 0.025 0.075 0.125 0.175 0.225
% Abs. % Abs. % Abs. % Abs. % Abs.
1 6.01 0.493 8.20 0.538 10.21 0.578 12.61 0.619 14.27 0.652

2 8.15 0.479 10.21 0.517 12.40 0.559 14.66 0.599 16.92 0.630

3 8.15 0.460 10.21 0.509 12.40 0.549 14.66 0.589 18.91 0.611

Table 7: Albumin content (%) and absorption of solution (Abs.) per hour, of modified resin containing 1.5mole of
acrylic acid monomer at pH=2.2, Temp.=310K
Time Concentration of albumin
(hour) 0.025 0.075 0.125 0.175 0.225
% Abs. % Abs. % Abs. % Abs. % Abs.
1 8.15 0.471 10.21 0.519 12.1 8 0.559 14.27 0.599 16.65 0.631

2 10.21 0.455 12.18 0.499 14.07 0.539 16.02 0.579 18.73 0.612

3 10.21 0.440 12.18 0.489 14.07 0.529 16.02 0.569 20.35 0.592

Table 8: Release of albumin per hour, of modified resin containing 0.5 mole of acrylic acid monomer at pH=8.0, Temp.
=310K
Time Absorbance
(hour) Concentration of albumin
0.025 0.075 0.125 0.175 0.225
1 0.133 0.166 0.188 0.209 0.223
2 0.144 0.174 0.196 0.219 0.232
3 0.152 0.184 0.206 0.229 0.244
4 0.165 0.196 0.219 0.239 0.252
5 0.165 0.196 0.219 0.239 0.263

Table 9: Release of albumin per hour, of modified resin containing 1.0 mole of acrylic acid monomer at pH=8.0,
Temp.=310K
Time Absorbance
(hour) Concentration of albumin
0.025 0.075 0.125 0.175 0.225
1 0.149 0.175 0.195 0.218 0.233
2 0.157 0.183 0.205 0.227 0.243

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 Zahraa Mushtaq Abd Al-Aama et. al.: Journal of Global Pharmacy Technology. 2017; 12(9):50-56

3 0.163 0.193 0.214 0.237 0.252

4 0.177 0.206 0.227 0.249 0.262
5 0.177 0.206 0.227 0.249 0.276

Table 10: Release of albumin per hour, of modified resin containing 1.5 mole of acrylic acid monomer at pH=8.0,
Temp.=310K
Time Absorbance
(hour) Concentration of albumin
0.025 0.075 0.125 0.175 0.225
1 0.159 0.185 0.205 0.228 0.242
2 0.168 0.194 0.213 0.237 0.251
3 0.177 0.201 0.224 0.247 0.263
4 0.189 0.214 0.236 0.259 0.272
5 0.189 0.214 0.236 0.259 0.285

Table 11: Release of albumin per hour, of modified resin containing 0.5 mole of acrylic acid monomer at pH=2.2,
Temp. =310K
Time Absorbance
(hour) Concentration of albumin
0.025 0.075 0.125 0.175 0.225
1 0.089 0.115 0.135 0.152 0.177
2 0.099 0.125 0.146 0.162 0.185
3 0.099 0.125 0.146 0.162 0.194

Table 12: Release of albumin per hour, of modified resin containing 1.0 mole of acrylic acid monomer at pH=2.2,
Temp. =310K
Time Absorbance
(hour) Concentration of albumin
0.025 0.075 0.125 0.175 0.225
1 0.099 0.125 0.145 0.165 0.187
2 0.109 0.136 0.158 0.174 0.196
3 0.109 0.136 0.158 0.174 0.206

Table 13: Release of albumin per hour, of modified resin containing 1.5 mole of acrylic acid monomer at pH=2.2,
Temp. =310K
Time Absorbance
( hour) Concentration of albumin
0.025 0.075 0.125 0.175 0.225
1 0.103 0.136 0.158 0.179 0.195
2 0.116 0.146 0.169 0.188 0.204
3 0.116 0.146 0.169 0.188 0.212

Conclusions observe that the protein loading in the base

In this work, a new co- polymer was prepared medium reaches the equilibrium state after
through the interaction of pentarythritol with five hours of immersion of the sample in the
fumaric acid to form a linear co- polymer base solution,But in the acid medium, the
containing four effective sites (double bond) protein load reaches the equilibrium state
able to bind to the double bond of monomer after a three hours in a maximum.
(acrylic acid monomer) to form three co-
polymers that differ among themselves in the From this we conclude that loading in the
number of active sites (double bond). basic medium is more efficient than loading
in the acid medium and it can be clearly
Thus, the density of the cross-linked will vary observed that the process of releasing the
in these polymers.Thus, swelling will be vary, albumin protein in the basic medium
this difference can be observed by loading (pH=8.0) is greater than the process of
and releasing of protein, the above release in the acid medium (pH=2.2), which
measurements can be said:It is possible to indicates the effectiveness of the co- polymer
on the release of protein in the basic medium
higher than in the acid medium.

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