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BY-NC-ND 3.0 license Open Access Published by De Gruyter April 28, 2016

Controlled synthesis and characterization of nanohydrogels formed from copolymer (2-acrylamido-2-methylpropane sulfonic acid/acrylamide)

Ahmed Awadallah-F, Soad Y. Abd El-Wahab and H.I. Al-Shafey
From the journal e-Polymers

Abstract

Nanohydrogels were prepared from copolymer 2-acrylamido-2-methylpropane sulfonic acid (AMPS)/acrylamide (AAm) in the presence of sodium lauryl sulfate (SLS) followed by γ-ray exposure. Different molar ratios of AMPS to AAm, 100:0 to 0:100, were investigated. The particle sizes of nanohydrogels were examined by high-resolution transmission electron microscopy (HR-TEM). The effects of different comonomer composition and pH on swelling (%) and gelation (%) were studied. The characterization of nanohydrogels was performed by Fourier transform infrared (FTIR) spectroscopy, energy dispersion X-ray (EDX), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The results indicate that particle sizes ranged from ~9.5 to ~39 nm.

1 Introduction

Nanohydrogels can be prepared by various self-assembly nanoparticle technologies, such as solvent emulsion, diffusion and precipitation methods (1). Nanohydrogels possess the unique properties of both hydrogels (i.e. a high loading ratio and high encapsulation efficiency in formulation of hydrophilic diagnostic and therapeutic agents) and nano-sized drug carriers (i.e. high cellular uptake due to their bulky size, which is suitable for internalization by cells via endocytosis) (24). In the process of endocytosis, the nanoparticles detach a small disk of bilayer from the cell membrane by sacrificing their surface energy to provide the edge energy of the disk, which is then converted to bending energy to allow the bilayer disk to be curved to envelope the nanoparticles and bring them into the cytoplasm. It has been shown by experiments, theoretical analysis and computer simulation that nanoparticles of 100–200 nm in size could have the highest cellular uptake efficiency. Therefore, it is easy to understand that nanoparticles that are too small may not have sufficient surface energy to overcome the bending energy needed for endocytosis. Moreover, too small nanoparticles would result in low drug encapsulation efficiency and fast drug release kinetics (5). The effect of size on cellular uptake of nanoparticles was confusing for many years. It was not until recently that the optimal size of nanoparticles for cellular drug delivery was shown to be 100–200 nm in diameter, which was determined by experimental measurement, theoretical analysis by membrane mechanics and thermodynamics (68). Endocytosis as a transportation mechanism has much higher efficiency than individual drug molecules for crossing the cell membrane. In fact, the bilayer membrane is a physical barrier to stop hydrophilic molecules from getting into cells. Nanohydrogels thus have all the advantages of other types of nanoparticles, such as micelles, liposomes, dendrimers, solid lipid nanoparticles and nanoparticles of biodegradable polymers, regarding efficient cellular delivery of diagnostic and therapeutic agents. Moreover, nanohydrogels are especially suitable for efficient delivery of hydrophilic small-molecule drugs, as well as biological drugs such as therapeutic proteins and peptides. Nanohydrogels exhibit features of nanoparticles and hydrogels. Therefore, they attracted more study in basic science. The potential applications of these nanohydrogels are in biotechnology, cosmetics, etc (9, 10). Furthermore, nanohydrogels have unique properties, such as swelling/deswelling behaviors and permeability of substances, when exposed to external stimuli (1113). Nanohydrogels, especially those sensitive to environmental changes, such as pH, temperature and other stimuli, have been under intensive investigation due to their great potential (1417). Lim et al. used a new injectable bone morphogenic protein-loaded alginate nanohydrogel to enhance osteoblastic growth and differentiation of human bone marrow stromal cells (18). Hong et al. used amine-terminated polyethylene glycol (PEG) thin films on silicon substrates to generate PEG nanohydrogels, which can bind different proteins covalently to create multifunctional surfaces for applications in emerging bio/proteomic and sensor technologies (19, 20). Additionally, the most popular temperature-sensitive nanohydrogels based on poly(N-isopropylacrylamine) (PNIPAAm) have gathered great interest. PNIPAAm hydrogels are known for their reversible swelling/deswelling behavior in response to temperature changes. When the temperature of their aqueous solution is below their lower critical solution temperature, nanohydrogels can remain in a swelling state and are capable of circulating through the bloodstream. However, the nanohydrogels become hydrophobic, aggregate easily and rapidly and deposit in heated tissues when the temperature rises (21).

In the present study, an attempt has been made to synthesize the nanohydrogels from 2-acrylamido-2-methylpropane sulfonic acid (AMPS) and acrylamide (AAm). Nanohydrogels have been characterized with high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), energy dispersion X-ray (EDX), thermogravimetric analysis (TGA) and swelling studies. Swelling behavior of the nanohydrogels has been studied as a function of reaction parameters used for the preparation of nanohydrogels. The swelling has also been carried out as a function of pH of the swelling medium. The influence of synthetic parameters, such as comonomer composition, total monomer concentration and a fixed sodium lauryl sulfate (SLS) concentration on the particle size of nanohydrogels, will be investigated to show how depth of these synthetic parameters has significant effects on the size of the nanoparticles of the formed hydrogels.

2 Experimental

2.1 Materials

AAm and AMPS were purchased from Sigma-Aldrich Chemical Co., (Merck, Germany) and SLS (Henkel, NJ, USA). Double distilled water was used for hydrogel preparation and swelling measurements. All reagents were of analytical grade unless otherwise stated.

2.2 Preparation of hydrogel

Radiation induced copolymerization of 20 wt% aqueous comonomer solutions of different compositions. The solutions were mixed well, transferred into small glass vials then irradiated from a 60Co source (Canada) at a dose rate ∼2.60 kGy/h and variable total dose that ranged from 5 to 30 kGy. The irradiation process was performed in air, at room temperature and a pressure of one bar. The optimum reaction conditions of coded samples and elemental compositions were listed in Table 1. After copolymerization, the vials were broken and the formed hydrogel cylinders were removed and cut into disks of 2 mm thickness and 5 mm diameter. All samples were washed with excess water and soaked overnight in distilled water to remove the unreacted components, then air dried at room temperature up to constant weight. The proposed reaction mechanism was depicted in Figure 1.

Table 1:

Optimum reaction conditions for the synthesis of copolymer (AMPS/AAm) nanohydrogels with 1% (wt/v) of sodium lauryl sulfate (SLS) via γ-rays at 30 kGy and a fixed dose rate of 2.60 kGy/h accompanied by dispersion X-ray analysis of elemental composition for different nanohydrogels.

Sample codeComposition ratioElemental composition (wt%)
AMPSAAmCONS
S-11000
S-2802055.4536.622.665.27
S-3604055.4336.683.064.83
S-4505055.4837.013.344.17
S-5406054.9737.343.853.84
S-6208056.6736.124.862.35
S-7010057.4936.256.26
Figure 1: The proposed reaction mechanism for the synthesis of copolymer (2-acrylamido-2-methylpropane sulfonic acid/acrylamide) nanohydrogel using γ-rays.

Figure 1:

The proposed reaction mechanism for the synthesis of copolymer (2-acrylamido-2-methylpropane sulfonic acid/acrylamide) nanohydrogel using γ-rays.

2.3 Characterizations

The morphological examination of the nanohydrogel of copolymer (AMPS/AAm) was conducted by HR-TEM analysis and was performed using a JEOL TEM-2100 electron microscope operating at an accelerating voltage of 200 kV (Japan). The samples were placed on a carbon-coated copper grid for TEM observation. Infrared (IR) spectroscopy measurements were carried out with the nanohydrogel of copolymer (AMPS/AAm). Prior to the assay, KBr was gently triturated with the dried samples (2% of polymer) and compressed into disks. FTIR spectra were obtained using an IR Prestige-21 spectrometer (Shimadzu, Japan) in the 4000–400 cm-1 region at room temperature. Thermogravimetric analysis was carried out using a Shimadzu TGA-50 thermogravimetric analyzer (Kyoto, Japan). This technique was carried out with a heating rate of 10°C/min with a temperature program from 25 to 800°C under nitrogen flow at a rate of 50 ml/min. X-ray diffraction (XRD) (Tokyo, Japan) was used to examine the crystal structure and was carried out by using a Rigaku X-ray generator (Cu Kα radiation with λ=1.54 A) with a scanning rate of 2o/min at room temperature. The surface morphology of the samples was observed by SEM model JOEL (JSM-6400) coupled with an energy dispersive-X-ray detector (Kyoto, Japan).

3 Results and discussion

3.1 Swelling and gel fraction

Figure 2A shows the swelling kinetics of the different hydrogel samples S-2, S-3, S-4, S-5, S-6 and S-7. Broad observation leads to the conclusion that the swelling increases with increasing time. It was observed that the swelling percentage increases with increasing the content of poly(AMPS) into the gel matrix. It is well known that gel swelling depends on the charge density of materials used in the absorbency process. This is due to that the poly(AMPS) contains high charge density of different functional groups (i.e. –C=O, -OH, -NH, -SO2), which have hydrophilic affinity to absorb more H2O molecules from solutions. Consequently, the swelling equilibrium is verified by verifying the charge density of functional groups of the nanohydrogel used. The results indicate that S-2 shows the highest swelling (%) while S-7 corresponds to the lowest swelling (%). The general order of nanohydrogel samples with regard to swelling (%) is S-2>S-3>S-4>S-5>S-6>S-7. Figure 2B shows the effect of pH level of medium on swelling (%) of different nanohydrogel samples. It was seen that by decreasing the pH value, swelling (%) increases and highest swelling (%) occurred at pH of 3 and lowest swelling (%) occurred at pH of 7. The effect of pH value on nanohydrogel swelling is a clear and visible trend. Figure 2C shows the effect of comonomer composition on the gel fraction of the formed nanohydrogel. It was noticed that by increasing the content of AAm into the sol, the gelation (%) increases. This may be due to the easy crosslinking of AAm than AMPS during the irradiation process. It is also noteworthy to mention that the S-1 did not produce gel.

Figure 2: Various investigations executed on the copolymer (AMPS/AAm) nanohydrogel samples.(A) swelling kinetics at 25°C, (B) pH-dependent swelling, pH of 7, time of 50 min at 25°C and (C) effect of comonomer composition on gel fraction percentage. Sodium lauryl sulfate (SLS) concentration 1% (v/v), irradiation dose 30 kGy and a fixed dose rate 2.60 kGy/h.

Figure 2:

Various investigations executed on the copolymer (AMPS/AAm) nanohydrogel samples.

(A) swelling kinetics at 25°C, (B) pH-dependent swelling, pH of 7, time of 50 min at 25°C and (C) effect of comonomer composition on gel fraction percentage. Sodium lauryl sulfate (SLS) concentration 1% (v/v), irradiation dose 30 kGy and a fixed dose rate 2.60 kGy/h.

3.2 Fourier transform infrared spectroscopy

Figure 3A and B illustrates two different compositions of copolymer (AMPS/AAm) nanohydrogel samples for 80:20 and 20:80 molar ratios, respectively. The presence of the functional groups of the copolymer (AMPS/AAm) nanohydrogel was evaluated by FT-IR spectra (Figure 3). Both spectra show a broad coupling peak of N-H and O-H stretching at around 3000–3500 cm-1, peaks of C-H stretching of CH and CH2 at around 2900–3000 cm-1, a sharp peak of C=O stretching of amide I at around 1663 cm-1 (Figure 3A) and 1664 cm-1 (Figure 3B) and a strong peak of the N-H bending of amide II at 1552 cm-1 (Figure 3A) and 1542 cm-1 (Figure 3B). The relative weak peaks at 1450 cm-1 (Figure 3A) and 1453 cm-1 (Figure 3B) along with those at 1663 cm-1 and 1664 cm-1 are the symmetrical and asymmetrical C(=O)2 stretching. The sharp and strong peaks of the S=O stretching of poly(AMPS) at 1037 cm-1 (Figure 3A) and 1043 cm-1 (Figure 3B) were observed, respectively (22, 23). Another two strong and sharp peaks at 1176 cm-1 (Figure 3A) and 1182 cm-1 (Figure 3B) arose from the C-C (=O)-O stretching.

Figure 3: FTIR spectra of (A) S-2 and (B) S-6 nanohydrogel samples.

Figure 3:

FTIR spectra of (A) S-2 and (B) S-6 nanohydrogel samples.

3.3 Surface morphology and elemental analysis

Figure 4A–F show the photomicrographs by SEM of various nanohydrogel samples S-2, S-3, S-4, S-5, S-6 and S-7, respectively. It was observed that the photomicrograph of each nanohydrogel is different from one gel sample to another. The difference is due to the different composition of formed samples.

Figure 4: SEM photomicrographs of (A) S-2, (B) S-3, (C) S-4, (D) S-5, (E) S-6 and (F) S-7 nanohydrogel samples.

Figure 4:

SEM photomicrographs of (A) S-2, (B) S-3, (C) S-4, (D) S-5, (E) S-6 and (F) S-7 nanohydrogel samples.

3.4 XRD analysis

Figure 5A–C show the XRD patterns of copolymer (AMPS/AAm) nanohydrogels for S-2, S-3 and S-5, respectively. From the XRD pattern of copolymer (AMPS/AAm) nanohydrogel, a sharp peak can be observed at about 2θ=21°, this is a characteristic peak of poly(AMPS) and poly(AAm). However, the peak declined obviously in the patterns of Figure 5B and C, respectively. Further, Figure 5A shows the highest peak among the nanohydrogel samples. This is due to the decline of crystallinity of poly(AMPS) into copolymer (AMPS/AAm) nanohydrogels. In other words, the increase of poly(AAm) into the hydrogel matrix decreased the crystallinity of copolymer (AMPS/AAm) nanohydrogels.

Figure 5: X-ray diffraction patterns of (A) S-2, (B) S-3 and (C) S-5 nanohydrogel samples.

Figure 5:

X-ray diffraction patterns of (A) S-2, (B) S-3 and (C) S-5 nanohydrogel samples.

3.5 HR-TEM photomicrograph analyses

The effect of comonomer composition on the photomicrograph of copolymer (AMPS/AAm) nanohydrogel is shown in Figure 6A–D for S-2, S-4, S-6 and S-7, respectively. It was observed that with an increasing concentration of AAm into the feeding composition, the resulting nanohydrogel particle size decreased. Thereafter, a high concentration of AAm into the feed composition not only has an irrelevant effect on nanohydrogel particle size, but also obliterates the features of nanoparticle sizes as shown in Figure 6D. Further, it was seen at a low concentration of AMPS into the feed composition of (AMPS/AAm) that the nanoparticles assemble in clusters as shown in the photomicrographs of Figure 6A and B. In Figure 7A–D, the particle size distribution of the nanohydrogel was measured in acetone at 25°C by HR-TEM, showing that the number average diameter of nanoparticle size ranged between ~9.5 and ~111.5 nm of formed nanohydrogels.

Figure 6: HR-TEM photomicrographs of nanohydrogel samples of (A) S-2, (B) S-4, (C) S-6 and (D) S-7.

Figure 6:

HR-TEM photomicrographs of nanohydrogel samples of (A) S-2, (B) S-4, (C) S-6 and (D) S-7.

Figure 7: Particle size distribution of different nanohydrogel samples prepared with various comonomer compositions of AMPS/AAm for (A) S-2, (B) S-4 and (C) S-6. (D) The relationship between concentration of comonomer and number average diameter of particle size of nanohydrogel.Total monomer concentration 20% (wt/v), irradiation dose 30 kGy and a fixed dose rate 2.6 kGy/h.

Figure 7:

Particle size distribution of different nanohydrogel samples prepared with various comonomer compositions of AMPS/AAm for (A) S-2, (B) S-4 and (C) S-6. (D) The relationship between concentration of comonomer and number average diameter of particle size of nanohydrogel.

Total monomer concentration 20% (wt/v), irradiation dose 30 kGy and a fixed dose rate 2.6 kGy/h.

Figure 8A–E show the photomicrographs of different nanohydrogel samples under the effect of total monomer concentration. Generally, it was observed that the particle size of nanohydrogels increases with increasing total monomer concentration. Moreover, the pore size among nanoparticles increases with increasing total concentration of monomers. It was observed that at a low total concentration of monomers, the nanoparticles assemble in clusters. Figure 9A–E show the particle size distribution of different nanohydrogel samples at various total monomer concentrations. As a general summary of the depicted results, the number average diameter of nanoparticle sizes increased from ~9.5 to ~39 nm according to the feed monomer concentration from 20% to 40% (wt/v), respectively. Figure 9F shows the relationship between the nanoparticle size of hydrogel and total monomer concentration of AMPS/AAm. It was observed that there is a direct proportional relation between the nanoparticle size and concentration. Furthermore, the trend of this relationship tends to be linear shape.

Figure 8: HR-TEM photomicrographs of nanohydrogels prepared at different total concentration of monomers (wt/v%): (A) 20, (B) 25, (C) 30, (D) 35 and (E) 40.One percentage (v/v) of sodium lauryl sulfate (SLS), feeding composition of AMPS/AAm 80:20 molar ratio, exposure irradiation dose 30 kGy and a fixed dose rate 2.6 kGy/h.

Figure 8:

HR-TEM photomicrographs of nanohydrogels prepared at different total concentration of monomers (wt/v%): (A) 20, (B) 25, (C) 30, (D) 35 and (E) 40.

One percentage (v/v) of sodium lauryl sulfate (SLS), feeding composition of AMPS/AAm 80:20 molar ratio, exposure irradiation dose 30 kGy and a fixed dose rate 2.6 kGy/h.

Figure 9: Particle size distribution of different nanohydrogel samples prepared with various concentrations (wt/v%): (A) 20, (B) 25, (C) 30, (D) 35 and (E) 40. (F) The relationship between total concentration of monomers and number average diameter of particle size of nanohydrogel.

Figure 9:

Particle size distribution of different nanohydrogel samples prepared with various concentrations (wt/v%): (A) 20, (B) 25, (C) 30, (D) 35 and (E) 40. (F) The relationship between total concentration of monomers and number average diameter of particle size of nanohydrogel.

4 Conclusions

Nanohydrogels were prepared from AMPS and AAm using gamma irradiation. Effects of comonomer composition, of total comonomer concentration and of SLS concentration on nanohydrogel particle size were examined. Generally, through the results, it was observed that the swelling (%) and the gelation (%) were affected by pH value and feed comonomer composition, respectively. The results indicated that both swelling (%) and gelation (%) of nanohydrogels were affected by the pH value of sol medium and feed composition of comonomer as well. The synthesized nanohydrogels were characterized by FTIR spectroscopy, EDX, SEM, TGA and HR-TEM techniques. The influence of synthetic parameters on the nanoparticle size properties was investigated. It was deduced from particle size distribution that the number average diameter of nanoparticle size ranged from ~9.5 to ~39 nm as a function of total monomer concentration and also that the number average diameter of nanoparticle size ranged from ~9.5 to ~111.5 nm as a function of comonomer composition. Consequently, the comonomer composition, total monomer concentration and a fixed concentration of SLS affect significantly the particle size of nanohydrogels formed. Therefore, it could be suggested that these nanohydrogels could be exploited in nanotechnology fields such as biomedical technologies, drug delivery systems and others.

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Received: 2015-11-24
Accepted: 2016-3-15
Published Online: 2016-4-28
Published in Print: 2016-5-1

©2016 by De Gruyter

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