European Polymer Journal 49 (2013) 601–612

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European Polymer Journal

journal homepage: www.elsevier.com/locate/europolj

Macromolecular Nanotechnology

Controlling the size and swellability of stimuli-responsive

polyvinylpyrrolidone–poly(acrylic acid) nanogels synthesized
by gamma radiation-induced template polymerization
Hassan A. Abd El-Rehim a,⇑, El-Sayed A. Hegazy a, Ashraf A. Hamed b, Ahmed E. Swilem b
a
Department of Polymers, National Center for Radiation Research and Technology, Nasr City, Cairo 11371, Egypt
b
Department of Chemistry, Faculty of Science, Ain Shams University, Abbassia, Cairo 11566, Egypt

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

Article history: Polymeric pH-sensitive hydrogel nanoparticles (nanogels) of narrow size distributions
Received 28 May 2012 were directly prepared by gamma radiation-induced polymerization of acrylic acid (AAc)
Received in revised form 7 December 2012 in an aqueous solution of polyvinylpyrrolidone (PVP) as a template polymer. The driving
Accepted 9 December 2012
force of PVP/PAAc nanoparticles formation was attributed to the complexation between
Available online 20 December 2012
PAAc (proton-donor) and PVP (proton-acceptor) through the hydrogen bonding interac-
tion. In addition to the hydrogen bonding interaction between the components, the nano-
Keywords:
particles are further stabilized by covalent bonds as a result of the radiation-induced
Nanogel
Gamma radiation
crosslinking process. Particle size and swellability of the prepared nanogels can be con-
Polyvinylpyrrolidone trolled by feed composition and concentration, PVP molecular weight as well as irradiation
Template dose, temperature, and atmosphere. The prepared PVP/PAAc nanogel particles were char-
pH-sensitive acterized by dynamic light scattering (DLS), viscometry, transmission electron microscopy
Interpolymer complex (TEM) and atomic force microscopy (AFM) techniques.
Ó 2012 Elsevier Ltd. All rights reserved.

1. Introduction concept of interpolymer complexation via hydrogen

Recently, there is a growing interest in synthesis and
design of soft nanomaterials to be applied in the biomedi-
cal field. Among these materials, hydrogel nanoparticles
have gained considerable attention due to their tunable
dimensions, large surface area, stable interior network
structure, and fast response to environmental factors, such
as ionic strength, pH, and temperature. These properties
demonstrate the great potential of nanogels for bio-related
applications such as drug delivery systems (DDS) and bio-
imaging [1–6].
Majority of methods utilized for nanogel synthesis are
often performed in microemulsion in order to prevent for-
mation of bulk material [7,8]. However, the formation of
hydrogel nanoparticles without using organic solvents
and surfactants is considered a challenge. Recently, the
⇑ Corresponding author. Tel.: +20 2 22872451; fax: +20 2 2749298.
E-mail address: ha_rehim@hotmail.com (H.A. Abd El-Rehim).
bonding has been exploited for this purpose [9]. Hydro-
gen-bonded interpolymer complexes (IPCs) are formed
between proton-donating poly(carboxylic acids) and pro-
ton-accepting non-ionic polymers. An interesting example
which has attracted a continuing interest as a model of
biological systems is the formation of polymer complexes
between poly(ethylene oxide) and poly(acrylic acid) via
H-bonding in aqueous media. These complexes are novel
individual compounds and their properties are entirely dif-
ferent from the properties of their component polymers.
Moreover, they are pH-sensitive since their formation de-
pends on the degree of ionization of the poly(carboxylic
acid) and thus on the environmental pH.
In the literature, different strategies to obtain nanogels
based on hydrogen-bonded IPCs have been studied. For
example, Liao et al. have reported a surfactant-free synthe-
sis of poly(acrylic acid) nanogels based on its complexation
with Hydroxypropylcellulose (HPC) [10]. The method in-
volved polymerization of acrylic acid in the presence of

0014-3057/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.eurpolymj.2012.12.002
 602 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612
HPC as a template and N,N0 -methylenebisacrylamide as a
crosslinking agent. Dou et al. have demonstrated the possi-
bility of preparation of hollow spheres and microgels based
on graft-copolymer of hydroxyethylcellulose-g-polyacrylic
acid [11]. Under acidic conditions, this graft-copolymer
formed intramolecular complex stabilized by hydrogen
bonding. This complex was then chemically crosslinked.
By controlling the reaction time and the amount of cross-
linking agent, particles of typical microgel structure were
obtained. Peppas group applied microemulsion and surfac-
tant-free emulsion method to the UV-induced synthesis of
micro- and nanoparticles based on poly(methacrylic acid)–
graft-poly(ethylene glycol) (PMAA–g-PEG) [12–14]. Pulse
radiolysis for IPC nanogel formation was also investigated.
Henke et al. reported an approach that involved irradiation
of PVP–PAAc complexes by pulses of fast electrons in di-
lute, deoxygenated solutions [15]. The radiation treatment
of IPC induces intramolecular (intracomplex) crosslinking
leading to the formation of permanent PVP–PAAc nanogels.
Practically, nanogels produced by this method are espe-
cially well suited for biomedical applications because they
MACROMOLECULAR NANOTECHNOLOGY
are free of residual toxic chemicals, e.g. monomers, initia-
tors or crosslinkers, and there is no need for additional
purification steps.
In fact, the use of gamma rays to form nanogels is very
limited. Thus, this study aims to develop a simple and effi-
cient method of producing nano-sized gel particles based
on hydrogen-bonded IPCs using gamma radiation. In this
regard, acrylic acid in an aqueous solution of polyvinylpyr-
rolidone (PVP) as a template polymer was exposed to gam-
ma rays to produce chemically crosslinked PVP/PAAc
nanogels. The method does not involve any organic sol-
vent, surfactant, crosslinker or chemical initiator. Many
parameters affecting the nanogel products were investi-
gated in order to have a successful production of pH sensi-
tive nanogel particles with controlled size and crosslinking
density. Characterization of the PVP/PAAc nanogels is car-
ried out, including morphological structure and equilib-
rium swelling studies.
2. Experimental section
2.1. Materials
Polyvinylpyrrolidone (PVP; K16–18, Mw = 8000; K29–
32, Mw = 58,000; K85–95, Mw = 1,300,000) and acrylic acid
(AAc) were obtained from Acros Organics (Belgium), and
were used as received. All reagents were of analytical grade
and were used without any purification. Deionized water
was used in all experiments.
2.2. Preparation of PVP/PAAc hydrogel nanoparticles
PVP/PAAc hydrogel nanoparticles were prepared via
gamma radiation-induced polymerization of AAc in an
aqueous solution of PVP. Aqueous solutions containing dif-
ferent feed compositions of PVP/AAc mixtures were intro-
duced into glass bottles and subjected to c-rays generated
from a 60Co source provided with a temperature control
unit at a dose rate of 3.85 kGy/h. The irradiation process
was carried out at 35 °C under air atmosphere; otherwise
conditions will be mentioned. In some cases, the feed solu-
tions were purged with nitrogen or nitrous oxide for
20 min to remove the dissolved oxygen, and then the bot-
tles were sealed and irradiated. To calculate the yield of
nanoparticles, the colloidal nanogel suspensions were cen-
trifuged (SORVALLÒ ULTRA 80, USA) at 20,000 rpm for
30 min. at 4 °C. Supernatants as well as aggregated nano-
gels were collected and freeze-dried in order to determine
the weight of the polymers which formed nanogels. The
production yields were calculated from the mass ratio of
polymers forming nanogel and the polymer and monomer
initially introduced in the preparation procedure.
2.3. Particle size measurements
Particle sizes of PVP/PAAc nanogels were measured by
the dynamic light scattering (DLS) technique using a PSS-
NICOMP Zeta Potential/Particle Sizer 380ZLS (PSS-NICOMP,
Santa Barbara, CA, USA). Samples were properly diluted
with freshly prepared deionized water (filtered with a
0.2 lm syringe filter) until an intensity of 250–350 kHz
was achieved. The dilutions were also convenient to avoid.
particle interactions. The pH of the solutions was adjusted
by adding few drops of NaOH or HCl. The scattered light
intensity was detected at a 90° angle and measurements
were run for at least 10 min. The volume-weighted hydro-
dynamic mean diameters were reported to know the size
contributing the most volume. The polydispersity index
(PDI) (the square of the coefficient of variation) which is
a measure of the size distribution breadth was also
calculated.
2.4. FT-IR spectrum analysis
FT-IR spectra of PVP, PAAc and freeze-dried PVP/PAAc
nanogel as KBr pellets were recorded by a JASCO FT/IR-
6300 spectrometer in the range of 400–4000 cm1.
2.5. UV–Vis measurements
To follow the formation of PVP/PAAc complexes, solu-
tions were analyzed by measuring the change in transmit-
tance at 500 nm using a JASCO UV/VIS spectrophotometer
V-560.
2.6. Viscosity measurements
Viscosity measurements were conducted at
30.0 ± 0.5 °C using Ubbelohde viscometer. The pH of the
solutions was adjusted by adding few drops of NaOH or
HCl. Deionized water was used as a reference solvent.
2.7. Morphology study
Transmission electron microscopy (TEM; JEOL JEM-
100CX, Japan) and atomic force microscopy (AFM; Agilent
AFM 5500, USA) were used to observe the morphology of
nanogel particles. For TEM observations, the nanogel sus-
pension was properly diluted and dripped onto carbon-
coated copper grid and then dried at room temperature.
 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612
For AFM observations, one drop of properly diluted nano-
gel suspension was placed on the surface of freshly cleaved
mica and then dried at room temperature.
3. Results and discussion
3.1. Radiation preparation of PVP/PAAc nanogel particles
It is well known that poly(acrylic acid) (PAAc) forms
interpolymer complexes (IPCs) with polyvinylpyrrolidone
(PVP) via H-bonding in aqueous media (co-operative ef-
fect) [15–21]. The interpolymer complex can be efficiently
formed only below a critical pH value which depends on
the molar ratios and molecular weights of the components.
When PAAc is mixed with PVP in aqueous phase at
pH < 4.00, a major conformational change occurs. At high
pH, higher than the pKa of PAAc (4.75), the majority of
the carboxyl groups of PAAc were ionized and hydrogen
bonding between the PAAc and PVP could not be main-
tained, resulting in a rapid IPC dissociation. Micellization
induced by complexation between PAAc and PVP may lead
to formation of nanoparticles when conducted at a low
concentration; otherwise, large irregular aggregates or
even precipitates will produce. This is because micelliza-
tion at a relatively high concentration occurs so rapidly
that there is no enough time for the soluble chains to dis-
entangle and adjust their conformation so as to surround
the insoluble aggregates, leading to larger and even irregu-
lar aggregates [22]. The technique of template polymeriza-
tion has the advantage of simultaneous polymerization
and self-assembly. In this technique the self-assembly be-
tween the components and their subsequent aggregation
can slow down. As a result, polymeric nanoparticles could
be produced at relatively high concentrations.
In this connection, trials were made to prepare PVP/
PAAc nanogels using PVP (Mw = 1,300,000) and AAc at mo-
lar ratio of 35/65 (mol% of PVP repeating unit per mol% of
AAc) and total concentration of 1.5%. Since PVP–PAAc com-
plexation in aqueous solution is always accompanied by a
change in its transparency [17], the variation in transmit-
tance (at 500 nm) of PVP/AAc solutions versus the irradia-
tion dose was studied to determine the critical dose at
which the PVP–PAAc complex is formed (Fig. 1). It was
found that at a dose of 0.5 kGy the feed solution changed
from transparent to slightly opaque (turbid). By increasing
the irradiation dose, the turbidity increases and reaches a
maximum at a dose of 1 kGy. Thereafter, any increase in
irradiation dose (more than 1 kGy), results in insignificant
changes in transmittance of PVP/AAc solutions. This means
that during the irradiation process (at a dose range of 0.5–
1 kGy) AAc molecules were polymerized and reached a
proper length for self-assembly with PVP. It is worth not-
ing that irradiation of PVP solution alone does not signifi-
cantly alter its transparency.
The dynamic light scattering technique (DLS) was also
used to measure the hydrodynamic mean diameter as well
as the polydispersity index of the produced particles at dif-
ferent pH values (4 and 7) in order to follow the permanent
structural changes caused by radiation and uniformity of
the prepared particles. Although nanoparticles are formed
at 1 kGy (as revealed from transparency changes of PVP/
603
100
80
60
%T
40
20
0
0 1 2 3 4 5
Dose (kGy)
Fig. 1. Changes of transmittance of PVP/AAc solution with irradiation
dose. Feed composition: 35/65 (PVP/AAc); feed conc.: 1.5%; PVP molec-
ular weight (Mw) = 1,300,000. Samples were diluted 5-fold with water.
AAc solution from transparent to opaque one upon irradia-
tion), the particles dissolved at pH 7, showing very broad
MACROMOLECULAR NANOTECHNOLOGY
size distributions similar to that of unirradiated PVP/AAc
feed solution (polydispersity index 0.4). This indicated
that there is no chemical crosslinking among the chains of
the particles prepared at low doses. However, at high irra-
diation doses (10–40 kGy), the PVP/PAAc particles did not
dissolve and instead they swelled. Fig. 2(a and b) shows
the size distribution (based on intensity, volume and num-
ber weighting) for PVP/PAAc particles formed at 20 kGy and
measured at pH 4 and 7, respectively. At pH 4, nanoparticles
with a mean diameter of 83 nm (volume-based) and a low
polydispersity index (0.041) were recorded. Meanwhile, at
pH 7, the particles expanded to 446 nm (volume-based)
with a slight increase in the polydispersity index (0.078).
Swelling of the nanoparticles occurred due to electrostatic
repulsion within the network caused by the ionization of
the carboxylic acid groups. At high pH values, the carbox-
ylic groups become ionized and the hydrogen bonds formed
between PAAc and PVP at low pH values are broken. The
low value of polydispersity index of irradiated PVP/PAAc
system as well as the convergent values of intensity, vol-
ume and number weighted mean diameters (at both pH 4
and 7) indicated that the prepared nanogel particles have
a monomodal distribution. The yield of the obtained PVP/
PAAc nanoparticles produced at 20 kGy was determined
to be very high (more than 90%).
3.2. Possible mechanism of PVP/PAAc nanoparticles formation
Since a dilute aqueous solution is used in this tech-
nique, the main part of radiation energy is absorbed by
water resulting in some reactive species (Reaction 1).
Ionizing radiation
H2 O ƒƒƒƒƒƒƒƒ!  OH;H ; eaq ; H3 Oþ ; H2 O2 ; H2 n ðReaction1Þ
Ionizing radiation and water radiolysis products, mainly
hydroxyl radicals and H-atoms, may generate a variety of
polymeric and monomeric reactive species, simulta-
neously. Accordingly, AAc may be homopolymerized and/
or grafted onto the PVP molecules when PVP macroradicals
recombine with oligomeric PAAc radicals or initiate the
 604 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612
MACROMOLECULAR NANOTECHNOLOGY

Fig. 2. Intensity (blue), volume (red) and number (green) weighted Gaussian distribution analysis for the PVP/PAAc nanogels at pH 4 (a) and 7 (b). Feed
composition: 35/65 (PVP/AAc); feed conc.: 1.5%; PVP molecular weight (Mw) = 1,300,000; 20 kGy. (For interpretation of the references to colour in this
figure legend, the reader is referred to the web version of this article.)

Scheme 1. Proposed scheme for radiation-induced formation of PVP/PAAc nanogel particles.

polymerization of AAc monomer. It was reported by Rai-
naldi et al. [20] that the polymerization of AAc in the pres-
ence of PVP as a template proceeds according to a pick-up
mechanism in which there is no preferential adsorption
between the monomer and the template because of the
weaker interactions, and polymerization starts in the bulk.
When the growing oligomer reaches a critical length, the
co-operative effects allow for the adsorption of the chain
on the template and the polymerization proceeds by
adding monomer from solution onto the growing chain
adsorbed on the template. Although the picture is more
complex here, it is possible to assume that PAAc chains,
 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612 605

MACROMOLECULAR NANOTECHNOLOGY
Fig. 3. FTIR spectra of PAAc, PVP and PVP/PAAc nanogel particles.

1400 600
pH 4 pH 7 (NaOH ) pH 4 Multimodal
pH 7 (NaOH) (0.239)
1200 (0.089) (nm) 500
2000 (0.078)
Mean diameter (nm)
Mean Diameter (nm)

1000 Multimodal
1500 (0.224) 400 (0.086)
(0.064)
800
1000
300
(0.078)
600 500

400 0 200
58,000 1,300,000
(0.015)
200 (0.035) (0.053) (0.041) (0.045)
(0.041) 100

0
8,000 58,000 1,300,000 0
PVP Molecular Weight Air/H2 O2 Air N 2O Nitrogen

Fig. 4. Effect of PVP molecular weight (Mw) on the particle size of the
prepared PVP/PAAc nanogels measured at pH 4 (main frame) and pH 7
(insert). Feed composition: 35/65 (PVP/AAc); feed conc.: 1.5%; 20 kGy.
Numbers inside parentheses represent polydispersity index (PDI).
Fig. 5. Effect of the environmental atmosphere during irradiation on the
particle size of the prepared PVP/PAAc nanogels at low and high pH. Feed
composition: 35/65 (PVP/AAc); feed conc.: 1.5%; PVP molecular weight
(Mw) = 1,300,000; 20 kGy. H2O2 conc.: 1% (based on feed conc.). Numbers
inside parentheses represent polydispersity index (PDI).

produced in situ, should reach a critical length in order to

self assemble with the template PVP molecules through
hydrogen bonding. Additionally, as nanoparticles are
formed and no macroscopic precipitation takes place in
this process, it could be suggested that the particles are
stabilized by some soluble polymer chains with less
complexed segments on their periphery (micelle-like
structure).
The initial pH of the feed solution plays an important
role in this process. The pH of the feed solution was mea-
sured to be below 4. If the feed solution pH is increased
over 4.5, the PVP/PAAc nanogels are not obtained. This is
due to the well known fact that the complex ability be-
tween PVP and PAAc decreases as the pH increases. It is
also noticed that the pH of the irradiated solution is
slightly shifted to a higher value due to the hydrogen
bonding (or interpolymer complexation) between PVP
and PAAc which decreases the ionization of latter. Further-
more, PVP may also change upon irradiation; if oxidized
and/or crosslinked. This may lead to change in its charge
and hydrophobicity. As PVP–PAAc complexation is not only
controlled by H-bonding, but also ion–dipole and hydro-
phobic interactions [23,24], eventual radiation-induced
modification of PVP may play a role. After most of mono-
mer molecules are polymerized and nanoparticles are
formed, the radiation energy can result in formation of rad-
ical centers on the polymer chains (both PVP and PAAc) in-
side the nanoparticles. It seems that these macroradicals
undergo predominantly crosslinking reactions producing
 606 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612

500 800
(0.112)
700
pH 4
400 pH7 (NaOH) (0.055)
Mean diameter (nm)

Mean Diameter (nm)

600
(0.078)
300 500
pH 7 (NaOH) (0.048)
pH 4 400 (0.102)
200 300

200 (0.066)
100 (0.051)
(0.04) (0.041) (0.041)
100

0 0
0 1 2 3 4 5 6 0.0 0.5 1.0 1.5 2.0 2.5 3.0
H2 O2 (wt %) Feed Concentration (wt %)
(based on feed concentration)
Fig. 8. Effect of feed concentration on the particle size of the prepared
PVP/PAAc nanogels at pH 4 and 7. Feed composition: 35/65 (PVP/AAc);
Fig. 6. Effect of H2O2 concentration on the particle size of the prepared
PVP 1,300,000; 20 kGy. Numbers inside parentheses represent polydis-
PVP/PAAc nanogels. Feed composition: 35/65 (PVP/AAc); feed conc.: 1.5%;
persity index (PDI).
PVP molecular weight (Mw) = 1,300,000; 20 kGy.
MACROMOLECULAR NANOTECHNOLOGY

PVP–g-PAAc nanogels. This suggestion is based on previous in the C@O region, at 1630 and 1727 cm1 which can be
work by the same technique using highly concentrated attributed to C@O from both components. The PAAc alone
feed solutions to produce PVP/PAAc copolymer hydrogels has a band at 1722 cm1, due to intermolecular hydrogen
[25]. Moreover, the relatively low polydispersity index at bonding between the carboxyl groups of PAAc. When PAAc
pH 7 in Fig. 2 confirms the formation of chemically stable and PVP form an interpolymer complex, some of the inter-
particles. The mechanism of PVP/PAAc nanogel formation molecular hydrogen bonds break and new hydrogen bonds
was postulated as shown in Scheme 1. are formed between the carboxyl groups of PAAc and the
To confirm the formation of PVP/PAAc interpolymer carbonyl groups of PVP. Therefore, once an interpolymer
complex, the FTIR spectra of PVP, PAAc and PVP/PAAc complex has formed, the carbonyl absorption band of PAAc
nanogel particles were recorded. As shown in Fig. 3, it is shifted to higher wave number at 1727 cm1 [18,19]. On
observed that the C@O for PVP and PAAc appears at 1661 the other hand, the carbonyl absorption band of PVP at
and 1722 cm1, respectively. Meanwhile, the FTIR spec- 1661 cm1 shifted to a lower wave number due to the
trum for PVP/PAAc complex shows two separated bands hydrogen bonds between the carboxyl groups of PAAc

240
700
220 (0.072) pH 7 (NaOH)
Mean diameter (nm)

(0.042)
600
200
500
(0.078)
Mean Diameter (nm)

180
400 (0.152)
160

300
140

120 200
25/75 35/65 55/45
100
(0.049)
80
(0.041) (0.036) (0.089)
pH 4
60

10 20 30 40 50 60 (PVP)
90 80 70 60 50 40 (AAc)

Feed Composition (PVP/AAc mol/mol %)

Fig. 7. Effect of feed composition on the particle size of the prepared PVP/PAAc nanogels at pH 4. Insert represents particle sizes at pH 7 for nanogels
prepared from three different feed compositions. Feed conc.: 1.5%; PVP 1,300,000; 20 kGy. Numbers inside parentheses represent polydispersity index
(PDI).
 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612 607

120
(0.049) (a) pH 4
Irradiated at ~35 0 C
800 pH ~ 4
100 Irradiated at ~10 0 C
(0.052) pH ~ 7
Mean diameter (nm)

(0.041) (0.117)

Mean diameter (nm)

(0.089)
80
600
(0.070) (0.208)
60
(0.078)
(0.048)
40 400 (0.058)

20
200
(0.04) (0.041) (0.037) (0.038)
0
25/75 35/65 55/45
Feed composition (PVP/AAc mol/mol %)
0
10 20 30 40
700
(b) pH 7 Irradiation dose (kGy)
(0.072) Irradiated at ~35 0 C
600
Irradiated at ~10 0 C Fig. 10. Effect of irradiation dose on the particle size of the prepared PVP/
Mean diameter (nm)

PAAc nanogels. Feed composition: 35/65 (PVP/AAc); feed conc.: 1.5%; PVP
500
(0.078) 1,300,000. Numbers inside parentheses represent polydispersity index
(0.120)
(PDI).

MACROMOLECULAR NANOTECHNOLOGY
400 (0.152)

300 (0.140)
2.6
(0.209)
200 2.4 20 kGy
40 kGy
100 2.2
Relative viscosity

2.0
0
25/75 35/65 55/45 1.8
Feed composition (PVP/AAc mol/mol %) 1.6

Fig. 9. Effect of irradiation temperature on the particle size of PVP/PAAc 1.4

nanogels prepared from different feed compositions when measured at
pH 4 (a) and pH 7 (b). Feed conc.: 1.5%; PVP 1,300,000; 20 kGy. Numbers 1.2
inside parentheses represent polydispersity index (PDI). 1.0

and the carbonyl groups of PVP in the PVP/PAAc complex. 0.8

3 4 5 6 7 8
These results obtained indicated that PAAc and PVP formed pH
a complex through hydrogen bonding by the radiation-
Fig. 11. Effect of irradiation dose on the relative viscosity of PVP/PAAc
nanogels at different pH values. Samples were diluted 5-fold with water.
Table 1 Feed composition: 35/65 (PVP/AAc); feed conc.: 1.5%, PVP 1,300,000.
Effect of irradiation temperature on the mean diameter of PVP/PAAc
nanogels prepared from PVP of different molecular weights.a
induced template polymerization of acrylic acid in the
PVP molecular Irradiation Mean diameter (nm) presence of PVP.
weight temperature (°C) (polydispersity index)
pH 4 pH 7 3.3. Factors affecting and controlling size and swellability of
(NaOH) PVP/PAAc nanogel particles
8000 10 441 N/A
(0.175) 3.3.1. Effect of PVP molecular weight
35 1191 N/A
Effect of PVP molecular weight (Mw) on the particle size
(0.089)
of the PVP/PAAc nanogels prepared by the ionizing radia-
58,000 10 65 356
tion was investigated as shown in Fig. 4. PVP of different
(0.036) (0.086)
35 136 1859 molecular weights (Mw = 8000, 58,000, 1,300,000) and
(0.035) (0.223) AAc were dissolved in water in order to obtain feed solu-
1,300,000 10 61 274 tions at molar ratio of 35/65 (mol% of PVP based on its
(0.061) (0.093) repeating units/mol% of AAc) and total concentration of
35 83 446 1.5%. The irradiation of a feed solution containing PVP of
(0.041) (0.078) Mw = 8000 resulted in PVP/PAAc particles of very large size
a
Feed composition: PVP/AAc (35/65 mol/mol%); feed concentration: accompanied by some insoluble precipitates. However,
1.5 wt.%; 20 kGy. nanosized PVP/PAAc particles were obtained when PVP of
 608 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612
MACROMOLECULAR NANOTECHNOLOGY

Fig. 12. Morphology of PVP/PAAc nanogel particles investigated in deionized water at pH 4. (a) TEM image without staining; (b) TEM image after staining
with uranyl acetate; (c) AFM image (topography and three dimensional). Feed composition: 35/65 (PVP/AAc); feed conc.: 1.5%; PVP 1,300,000; 20 kGy.

Mw = 58,000 or 1,300,000 was used. At pH 7 (Fig. 4, insert),
the particles obtained from PVP of Mw = 8000 could not be
measured at the same concentration; the scattered light
intensity from the sample was very low. The particles ap-
peared to be completely dissolved indicating that the
crosslinking yield among the particle chains during the
irradiation processing is limited. However, the particles
prepared from PVP of Mw = 58,000 or 1,300,000 underwent
a swelling behavior. In case of PVP of Mw = 58,000 the par-
ticles showed a very large increase in the mean diameter
with multimodal size distribution while the particles pre-
pared from PVP of Mw = 1,300,000 showed a relatively
low increase in the mean diameter with monomodal size
distribution.
PVP accomplishes the role of a template for the disper-
sion polymerization of AAc. But, beside the formation of an
interpolymer complex, which is the basis of the stabiliza-
tion mechanism of the formed PAAc, there may be a con-
current process involving PVP: radiation-induced
crosslinking and copolymerization with AAc/PAAc. The ob-
tained results indicate that the higher the PVP molecular
weight the higher the crosslinking yield among the poly-
mer chain segments within the particles (chemical stabil-
ity). The folding and tangling of the large PVP molecules
might allow the formation particles with interpolymer pe-
netrating network (IPN) structure producing nanogels of
more compact structure and smaller size. Moreover,
increasing the molecular weight of PVP might increase
the probability of the formation of the grafted complex
due to the viscosity effect in the reaction medium [21].
3.3.2. Effect of irradiation atmosphere
To investigate the effect of the environmental atmo-
sphere during irradiation on the particle size of the pre-
pared PVP/PAAc nanogels, a feed solution containing PVP/
AAc mixture at molar ratio of 35/65 and concentration of
1.5% was irradiated (20 kGy) under different atmospheres
such as nitrogen, nitrous oxide and air. Fig. 5 shows the
 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612 609

MACROMOLECULAR NANOTECHNOLOGY
Fig. 13. TEM and 3D AFM images of PVP/PAAc nanogel particles prepared by irradiation doses of 20 (a) and 40 (b) kGy, and deposited from an aqueous
solution at pH 7 without staining. Feed composition: 35/65 (PVP/AAc); feed conc.: 1.5%; PVP 1,300,000.

mean diameter of the particles produced in each case at
low and high pH values. It is clear that at pH 4 the mean
diameter of the PVP/PAAc particles prepared under nitro-
gen atmosphere is slightly higher than those of particles
prepared in the presence of air or nitrous oxide. At pH 7,
the particle sizes in all cases are higher than those mea-
sured at low pH. But the particles prepared under nitrogen
atmosphere do not maintain a monomodal size distribu-
tion if compared with the particles prepared under air or
nitrous oxide atmosphere.
According to Byakov et al., the dissolved oxygen affects
water radiolysis and leads to an additional increase in the
hydrogen peroxide (H2O2) yield [26]. H2O2 is retained in
water and reacts with the reducing species (e aq and H) to
produce OH radicals and corresponding species [27,28].
Therefore, under air atmosphere the yield of OH radicals
might increase in the solution, resulting in an increase in
the concentration of polymeric and monomeric reactive
species. This might decrease the length of the produced
PAAc chains and enhance the formation of the grafted
complex, forming small particles with chemically stable
interior network structure. Similar results were obtained
when the solutions are saturated by N2O. In this case, the
dissolved oxygen is removed and the hydrated electrons,
resulted from water radiolysis, are converted into addi-
tional OH radicals as described in Reaction Reaction 2. On
the other side, when oxygen is removed, by passing N2
gas through the reactant feed solution, it is expected that
the produced PAAc chains are relatively longer and the
crosslinking yield among the nanoparticle chains is rela-
tively low as indicated from their multimodal size distribu-
tion at high pH.
eaq þ N2 O !  OH þ OH þ N2 ðReaction2Þ
The effect of H2O2 was also studied by adding different
concentrations of H2O2 to the feed solution and irradiating
it under air atmosphere (Fig. 6). This can increase the con-
centration of OH radicals as a result of the interaction of
H2O2 with the reducing species. At low pH, there is no sig-
nificant change in the nanogel particle size at different
 610 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612
H2O2 concentrations. However, after swelling at high pH,
the size of the nanogel particles decreases slightly if com-
pared with that obtained in the absence of H2O2. It seems
that just small concentrations of H2O2 can help produce
nanogels of relatively lower swelling behavior while higher
concentrations (about over 10%) caused rather degradation
reactions and the particles dissolved at high pH.
3.3.3. Effect of feed composition
The feed composition plays an important role in con-
trolling the PVP/PAAc nanogel particle size (Fig. 7). In this
study, the reactants (PVP and AAc) were fed in different
molar ratios ranging from 15/85 to 55/45 (mol% of PVP
based on its repeating units/mol% of AAc) while their total
concentration is kept constant (1.5%). When the particle
size was measured at low pH, it was observed that nanogel
particles of large size were produced from the AAc-rich
feed solution. As the PVP/AAc molar ratio increased in
the feed solution, the particle size decreased sharply until
a PVP/AAc molar ratio of about 30/70 was reached. There-
after, PVP/AAc ratios in the range between 30/70 and 55/45
MACROMOLECULAR NANOTECHNOLOGY
did not affect significantly the particle size. Meanwhile, by
using molar ratios higher than 55/45 (PVP/AAc), multi-
modal particles and even an apparent macroscopic gel
phase (separated from the original liquid phase) were
obtained.
A higher concentration of AAc in the feed solution in the
expense of PVP may result in a higher concentration of
PAAc around PVP, which leads to a larger nanogel size.
However, as the concentration of PAAc increases, the poly-
meric components can quickly dehydrate and shrink as a
result of hydrogen bonding to form the nucleus of the
nanogels. This might explain the insignificant changes of
the particle size using molar ratios in the range between
30/70 and 55/45 (PVP/AAc). After the maximum complex-
ation is attained (at about 40/60 PVP/PAAc molar ratio
[17,29]), further increases in AAc concentration can cause
a sharp increase in the particle size. Therefore, the opti-
mum composition for production of nanogels of compact
structure and low particle size might contain about 50–
75 mol% of AAc. Also, the results revealed that the prepared
nanoparticles possess a narrow particle size distribution;
although those obtained from the PVP-rich feed solution
(PVP/AAc molar ratio of 55/45) have a relatively high poly-
dispersity index. This might be due to both the lake of
interpolymer complexation and presence of some soluble
uncomplexed PVP molecules (yield of nanoparticles was
relatively low, 80%).
Particle sizes of PVP/PAAc nanogels that prepared from
different feed compositions were also measured at pH 7
(Fig. 7, insert). By comparing the particle size at low and
high pH, it can be observed that the swelling degree of
the nanogel particles increases by increasing the AAc con-
tent in the feed solution, i.e. the higher the content of PAAc
in the particles the higher the swelling degree. At high pH
value, the carboxylic groups of PAAc chains become ion-
ized, resulting in dissociation of the H-bonded PVP/PAAc
interpolymer complexes and electrostatic repulsion be-
tween the ionized PAAc chain segments. Therefore, as the
PAAc content increases, the water-solubility of PVP/PAAc
chains is strengthened and a large amount of water
molecules penetrates the nanogel particles, resulting in
an increase in the swelling degree.
3.3.4. Effect of feed concentration
The feed concentration is another important parameter
through which the particle size of the prepared PVP/PAAc
nanogels can be controlled. Fig. 8 presents the effect of feed
concentration (from 0.5% to 2.5%) on the particle size of the
prepared PVP/PAAc nanogels at a constant feed composi-
tion. The particle size, except for the lowest feed concentra-
tion, increases with the increase of feed concentration when
measured at both low and high pH values (the effect is clear
at high pH). At high feed concentrations, the intermolecular
recombination of radicals which usually leads to an increase
in molecular weight and coil dimensions is promoted. How-
ever, the increase in size at the lowest feed concentration
may be due to the insufficient length of the produced PAAc
chains as well as the competition in hydrogen bonding
interactions between the polymer and the solvent, which
result in ineffective complexation and formation of dis-
torted nanogel structures of relatively large size.
3.3.5. Effect of irradiation temperature
Fig. 9 shows the effect of irradiation temperature on the
mean diameter of the PVP/PAAc nanogels prepared at dif-
ferent feed compositions. The size of PVP/PAAc nanogel
particles prepared at 10 °C is lower than that prepared
at 35 °C for all feed compositions when measured in
deionized water at pH 4 and 7. According to the basic the-
ory of radiation-induced polymerization, the polymeriza-
tion rate and the molecular weight of the resultant
polymer increase with the increase of temperature [30].
Thus, the molecular weight of the growing polymer (PAAc)
decreases at low temperature resulting in nanogel particles
of relatively small size. In addition, contribution of other
factors such as complexing ability, hydrophobic interac-
tions, and solution viscosity might be also possible [31].
It is mentioned above that PVP/PAAc nanogels of small
size and stable network structure could not be obtained
from PVP of low molecular weight at 35 °C and 20 kGy.
So, a trial was made to overcome this problem by irradiat-
ing the feed solutions at low temperature (10 °C). As
shown in Table 1, relatively smaller particles are obtained
from PVP of low molecular weights at low irradiation tem-
perature if compared with that obtained at high tempera-
ture. Meanwhile, PVP of Mw = 8000 is still unable to
produce chemically crosslinked nanogel particles.
3.3.6. Effect of irradiation dose
The particle size of the PVP/PAAc nanogels prepared at
different irradiation doses was investigated at low and
high pH values using the DLS technique (Fig. 10). There is
no significant change in the mean diameter of the PVP/
PAAc nanogels prepared at different doses when measured
at low pH. However, the particle size as well as the polydis-
persity index decreased with increasing the irradiation
dose when measured at high pH. At low pH, the swelling
of PVP/PAAc particles is very limited due to the strong
hydrogen bonding and interpolymer complex between
the polymer chains. Thus, the effect of irradiation dose
on the swelling behavior is not clear at low pH. The
 H.A. Abd El-Rehim et al. / European Polymer Journal 49 (2013) 601–612
interpolymer complex between the polymer chains disso-
ciates at high pH and the swelling behavior of the nanogel
particles will depend only on the crosslinking density ob-
tained at different irradiation doses. The higher the irradi-
ation dose, the higher the crosslinking degree and the
lower the swelling behavior as well as the particle size of
the PVP/PAAc nanogels.
In addition to the DLS results, the effect of irradiation
dose can also be studied by viscosity measurements. The
relative viscosity of the prepared PVP/PAAc nanogels pre-
pared under various irradiation doses was determined at
different pH values as shown in Fig. 11. The relative viscos-
ity increases as the pH of the medium increases. It can also
be noticed that at the same pH the relative viscosity of the
prepared nanogel decreases as the irradiation dose in-
creases. The strong hydrogen bonding between the poly-
mer chains of the PVP/PAAc nanogel at low pH leads to a
nanogel with compact structure and low viscosity. As men-
tioned before, when the pH increases, the PAAc chains be-
come ionized and the strong hydrogen bonding between
the PVP–g-PAAc chains becomes weakened leading to a re-
laxed structure. Thus, the water-solubility of the nanogel
chains is enhanced resulting in an increase in the relative
viscosity. However, the increase in the irradiation dose re-
sults in formation of covalent bonds between the chain
segments of the nanogel. This limits the mobility of these
segments and lowers the viscosity of the nanogel solution.
3.4. Morphology of PVP/PAAc nanogels
AFM and TEM are powerful tools for investigating the
morphology of nanoparticles. Fig. 12 shows the morphol-
ogy (at pH 4) of the PVP/PAAc nanogel particles prepared
from a feed solution containing PVP/AAc mixture at molar
ratio of 35/65 and total concentration of 1.5%, and exposed
to 20 kGy. It can be barely seen from the TEM image
(Fig. 12a) slightly deformed spherical particles of low con-
trast with diameters ranged from 70 to 150 nm. When the
nanogel particles were stained with uranyl acetate, adher-
ent spherical particles of better contrast with a core–shell
structure could be observed as shown in Fig. 12b. However,
staining of the nanogel particles resulted also in shrinkage
in their size. The spherical shape and mean diameter of the
nanogel particles were also confirmed by AFM measure-
ments (Fig. 12c). The AFM image shows that the particles’
heights (4–6 nm) are greatly smaller than their widths
(70–150 nm) suggesting substantial flattering of the par-
ticles on the mica.
Fig. 13 display the morphology of PVP/PAAc nanogel
particles prepared at irradiation doses of 20 and 40 kGy,
and deposited from aqueous solutions at pH 7. It can be no-
ticed that the pH value affects the size and shape of the
nanoparticles. The particles expanded upon increasing
the pH as a result of the deionization of the carboxlic
groups. The effect of irradiation dose on the nanogel parti-
cles can be easily seen by comparing their morphology. The
spherical shape of the nanogel particles prepared by an
irradiation dose of 20 kGy (Fig. 13a) is distorted after
swelling while the shape of particles prepared by an irradi-
ation dose of 40 kGy (Fig. 13b) is quite stable. The higher
crosslinking degree, obtained by using a higher irradiation
611
dose, results in the formation of more compact nanogel
particles, and thus their spherical shape is substantially
kept undistorted at high pH. The diameters of the nanogel
particles observed by both TEM and AFM, especially at pH
7, are smaller than those determined by DLS. This decrease
in size should be caused by the shrinkage of particles dur-
ing water evaporation in the sample preparation [11,32].
4. Conclusions
Chemically crosslinked, pH-sensitive PVP/PAAc hydro-
gel nanoparticles were successfully prepared in a high yield
via gamma radiation-induced polymerization of acrylic
acid in an aqueous solution of polyvinylpyrrolidone (PVP)
as a template polymer. The particle sizes of the PVP/PAAc
nanogels at different pH values were evaluated using
dynamic light scattering (DLS) and the morphology was
assessed using atomic force microscopy (AFM) and
transmission electron microscopy (TEM). Smaller and more
stable nanogel particles can be produced by irradiating a
feed solution containing about 50 to 75 mol% of AAc and
MACROMOLECULAR NANOTECHNOLOGY
using PVP of high molecular weight. The particle size
increases with the increase in feed concentration and the
suitable concentration might be from 1% to 2%. The nanogel
particles prepared under air or nitrous oxide atmosphere
were slightly smaller and more stable (lower polydispersity
index at high pH) than those prepared under nitrogen
atmosphere. The particle size can also be decreased by
lowering the irradiation temperature. Increasing the
irradiation dose decreased the swelling degree of the PVP/
PAAc nanogel particles. These nanoparticles (nanogels)
are expected to be potentially useful in drug delivery due
to their controllable sizes. Besides, the presence of carbox-
ylic groups enables the particles to adsorb cationic drugs or
to be conjugated with some bioactive molecules.
Acknowledgement
This work is supported by the International Atomic En-
ergy Agency (IAEA) regular budget fund under research
contract No. 15470/R1.
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