Nanocomposite Hydrogel Synthesis using Ultrasonication
Nanocomposite hydrogels or nanogels are multi-functional 3D structures with high efficacies as drug carriers and controlled-release drug delivery systems. Ultrasonication promotes the dispersion of nano-sized, polymeric hydrogel particles as well as the subsequent inclusion/incorporation of nanoparticles into these polymer structures.
Ultrasonic Synthesis of Nanogels
Nanocomposite hydrogels are three-dimensional material structures and can be designed to exhibit specific features, which makes them potent drug carriers and controlled-release drug delivery systems. Ultrasonication promotes the synthesis of functionalized nano-sized particles as well as the subsequent inclusion/incorporation of nanoparticles in three-dimensional polymeric structures. As ultrasonically synthesized nanogels can entrap bioactive compounds inside their nanoscale core, these nano-sized hydrogels offer great functionalities.
Nanogels are aqueous dispersion of hydrogel nanoparticles, which are physically or chemically cross-linked as hydrophilic polymer network. As high-performance ultrasound is highly efficient in producing nano-dispersions, probe-type ultrasonicators are a crucial tool for the fast and reliable production of nanogels with superior functionalities.
Functionalities of Ultrasonically Produced Nanogels
- excellent colloidal stability and the large specific surface area
- can be densely packed with nanoparticles
- allow to combine hard and soft particles in hybrid core/shell nanogel
- high hydration potential
- promoting bioavailability
- high swelling / de-swelling properties
Ultrasonically synthesized nanogels are used in numerous applications and industries, e.g.
- for pharmaceutical and medical applications: e.g. drug carrier, antibacterial gel, antibacterial wound dressing
- in biochemistry and biomedicine for gene delivery
- as adsorbent/biosorbent in chemical and environmental applications
- in tissue engineering as hydrogels can mimic the physical, chemical, electrical, and biological properties of many native tissue
Case Study: Zinc Nanogel Synthesis via Sonochemical Route
ZnO hybrid nanoparticles can be stabilized in a Carbopol gel via a facile ultrasonic process: Sonication is used to drive the precipitation of zinc nanoparticles, which are subsequently ultrasonically crosslinked with Carbopol to form a nano-hydrogel.
Ismail et al. (2021) precipitated zinc oxide nanoparticles via a facile sonochemical route. (Find the protocol for the sonochemical synthesis of ZnO nanoparticles here).
Subsequently, the nanoparticles were used to synthesize the ZnO nanogel. Therefore, the produced ZnO NPs were rinsed with double deionized water. 0.5 g of Carbopol 940 was dissolved in 300 mL of doubled deionized water, followed by addition of the freshly washed ZnO NPs. Since Carbopol is naturally acidic, the solution requires a neutralisation of the pH value, otherwise it would not thicken. Thus, the mixture had undergone continuous sonication using the Hielscher ultrasonicator UP400S with an amplitude of 95 and a cycle of 95% for 1 h. Then, 50 mL of trimethylamine (TEA) as a neutralizing agent (raising the pH to 7) was added dropwise under continuous sonication until the formation of the ZnO white gel occurred. The thickening of the Carbopol started when the pH was near to a neutral pH .
The research team explains the extraordinarily positive effects of ultrasonication on nanogel formation by enhanced particle-particle interaction. Ultrasonically initiated molecular agitation of the constituents in the reaction mixture enhances the thickening process promoted by the polymer-solvent interactions. Additionally, sonication promotes the dissolving of Carbopol. In addition, ultrasound wave irradiation enhances the polymer–ZnO NPs interaction and improves the viscoelastic properties of the prepared Carbopol/ZnO hybrid nanoparticles gel.
The schematic flowchart above shows the synthesis of ZnO NPs and Carbopol/ZnO hybrid nanoparticle gel. In the study, the ultrasonicator UP400St was used for ZnO nanoparticle precipitation and nanogel formation. (adapted from Ismail et al., 2021)
Case Stuy: Ultrasonic Preparation of Poly(methacrylic acid)/Montmorillonite (PMA/nMMT) Nanogel
Khan et al. (2020) demonstrated the successful synthesis of a poly(methacrylic acid)/Montmorillonite (PMA/nMMT) nanocomposite hydrogel via ultrasound-assisted redox polymerization. Typically, 1.0 g of nMMT was dispersed in 50 mL of distilled water with ultrasonication for 2 h to form a homogeneous dispersion. Sonication improves the dispersion of clay, resulting in enhanced mechanical properties and adsorption capacity of the hydrogels. Methacrylic acid monomer (30 mL) was added dropwise to the suspension. Initiator ammonium persulfate (APS) (0.1 M) was added to the mixture followed by 1.0 mL of TEMED accelerator. The dispersion was vigorously stirred for 4 h at 50°C by a magnetic stirrer. The resulting viscous mass was acetone-washed and desiccated for 48 h at 70°C in an oven. The resulting product was ground and stored in a glass bottle. Different nanocomposite gels were synthesized by varying the nMMT in quantities of 0.5, 1.0, 1.5, and 2.0 g. The nanocomposite hydrogels prepared using 1.0 g of nMMT depicted better adsorption results than the rest of composites and was therefore used for further adsorption investigation.
The SEM-EDX micrographs on the right show the elemental and structural analysis of the nanogels consisting in montmorillonite (MMT), nano-montmorillonite (nMMT), poly(methacrylic acid)/nano-montmorillonite (PMA/nMMT), and amoxicillin (AMX)- and diclofenac (DF)-loaded PMA/nMMT. The SEM micrographs recorded at a magnification of 1.00 KX along with the EDX of
- montmorillonite (MMT),
- nano-montmorillonite (nMMT),
- poly(methacrylic acid)/nano-montmorillonite (PMA/nMMT),
- and amoxicillin (AMX)- and diclofenac (DF)-loaded PMA/nMMT.
It is observed that raw MMT owes a layered sheet structure showing the presence of larger grains. After modification, the sheets of MMT are exfoliated into tiny particles, which may be due to the elimination of Si2+ and Al3+ from the octahedral sites. The EDX spectrum of nMMT exhibits a high percentage of carbon, which may primarily be due to the surfactant utilized for modification as the main constituent of CTAB (C19H42BrN) is carbon (84%). PMA/nMMT displays a coherent and near-co-continuous structure. Further, no pores are visible, which depicts the complete exfoliation of nMMT into the PMA matrix. After sorption with the pharmaceutical molecules amoxicillin (AMX) and diclofenac (DF), changes in the PMA/nMMT morphology are observed. The surface becomes asymmetric with an increase in the rough texture.
Use and functionalities of clay-based nano-sized hydrogels: Clay-based hydrogel nanocomposites are envisioned to be potential super adsorbents for the uptake of inorganic and/or organic contaminants from an aqueous solution due to the combining characteristics of both clays and polymers, such as biodegradability, biocompatibility, economic viability, abundance, high specific surface area, three-dimensional network, and swelling / de-swelling properties.
(cf. Khan et al., 2020)
High Performance Ultrasonicators for Hydrogel and Nanogel Production
High Performance Ultrasonicators for Hydrogel and Nanogel Production
Hielscher Ultrasonics manufactures high-performance ultrasonic equipment for the synthesis of hydrogels and nanogels with superior functionalities. From small and mid-size R&D and pilot ultrasonicators to industrial systems for commercial hydrogel manufacturing in continuous mode, Hielscher Ultrasonics has the right ultrasonic processor to cover your requirements for hydrogel / nanogel production.
- high efficiency
- state-of-the-art technology
- reliability & robustness
- batch & inline
- for any volume
- intelligent software
- smart features (e.g., data protocolling)
- easy and safe to operate
- low maintenance
- CIP (clean-in-place)
The table below gives you an indication of the approximate processing capacity of our ultrasonicators:
|Batch Volume||Flow Rate||Recommended Devices|
|1 to 500mL||10 to 200mL/min||UP100H|
|10 to 2000mL||20 to 400mL/min||UP200Ht, UP400St|
|0.1 to 20L||0.2 to 4L/min||UIP2000hdT|
|10 to 100L||2 to 10L/min||UIP4000hdT|
|15 to 150L||3 to 15L/min||UIP6000hdT|
|n.a.||10 to 100L/min||UIP16000|
|n.a.||larger||cluster of UIP16000|
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Literature / References
- Ismail, S.H.; Hamdy, A.; Ismail, T.A.; Mahboub, H.H.; Mahmoud, W.H.; Daoush, W.M. (2021): Synthesis and Characterization of Antibacterial Carbopol/ZnO Hybrid Nanoparticles Gel. Crystals 2021, 11, 1092.
- Khan, Suhail; Fuzail Siddiqui, Mohammad; Khan, Tabrez Alam (2020): Synthesis of poly(methacrylic acid)/montmorillonite hydrogel nanocomposite for efficient adsorption of Amoxicillin and Diclofenac from aqueous environment: Kinetic, isotherm, reusability, and thermodynamic investigations. ACS Omega. 5, 2020. 2843–2855.
- Rutgeerts, Laurens A. J.; Soultan, Al Halifa; Subramani, Ramesh; Toprakhisar, Burak; Ramon, Herman; Paderes, Monissa C.; De Borggraeve, Wim M.; Patterson, Jennifer (2019): Robust scalable synthesis of a bis-urea derivative forming thixotropic and cytocompatible supramolecular hydrogels. Chemical Communications Issue 51, 2019.
Facts Worth Knowing
Protocol for Sonochemical Synthesis of ZnO Nanoparticles
ZnO NPs were synthesized using the chemical precipitation method under the effect of ultrasound irradiation. In a typical procedure, zinc acetate dihydrate (Zn(CH3COO)2·2H2O) as a precursor, and an ammonia solution of 30–33% (NH3) in an aqueous solution (NH4OH) as a reducing agent, were used. The ZnO nanoparticles were produced by dissolving the appropriate amount of zinc acetate in 100 mL of deionized water to produce 0.1 M of a zinc ions solution. Subsequently, the zinc ions solution was subjected to ultrasonic wave irradiation using a Hielscher UP400S (400 W, 24 kHz, Berlin, Germany) at an amplitude of 79% and a cycle of 0.76 for 5 min at a temperature of 40 ◦C. Then, the ammonia solution was added dropwise to the zinc ions solution under the effect of the ultrasonic waves. After few moments, the ZnO NPs began to precipitate and grow, and the ammonia solution was continuously added until the complete precipitation of ZnO NPs occurred.
The obtained ZnO NPs were washed using deionized water several times and were left out to settle down. Posteriorly, the obtained precipitate was dried at room temperature.
(Ismail et al., 2021)
What are Nanogels?
Nanogels or nanocomposite hydrogels are a type of hydrogel that incorporates nanoparticles, usually in the range of 1-100 nanometers, into their structure. These nanoparticles can be organic, inorganic, or a combination of both.
Nanogels are formed through a process known as crosslinking, which involves the chemical bonding of polymer chains to form a three-dimensional network. Since the formation of hydrogels and nanogels requires thorough mixing in order to hydrate the polymeric structure, to promote the crosslinking and to incorporate the nanoparticles, ultrasonication is a highly efficacious technique for the production of hydrogels and nanogels. Hydrogel and nanogel networks are capable of absorbing large amounts of water, making nanogels highly hydrated and thus suitable for a wide range of applications such as drug delivery, tissue engineering, and biosensors.
Nanogel hydrogels are typically composed of nanoparticles, such as silica or polymer particles, that are dispersed throughout the hydrogel matrix. These nanoparticles can be synthesized through various methods, including emulsion polymerization, inverse emulsion polymerization, and sol-gel synthesis. These polymerization and sol-gel syntheses benefit greatly from ultrasonic agitation.
Nanocomposite hydrogels, on the other hand, are composed of a combination of a hydrogel and a nanofiller, such as clay or graphene oxide. The addition of the nanofiller can improve the mechanical and physical properties of the hydrogel, such as its stiffness, tensile strength, and toughness. Here, the powerful dispersion capacities of sonication facilitate the uniform and stable distribution of nanoparticles into the hydrogel matrix.
Overall, nanogel and nanocomposite hydrogels have a wide range of potential applications in fields such as biomedicine, environmental remediation, and energy storage due to their unique properties and functionalities.
Applications of Nanogel for Medical Treatments
|Type of Nanogel||Drug||Disease||Activity||References|
|PAMA-DMMA nanogels||Doxorubicin||Cancer||Increase in the release rate as the pH value decreased. Higher cytotoxicity at pH 6.8 in cell-viability studies||Du et al. (2010)|
|Chitosan-based nanogels decorated with hyaluronate||Photosensitizers like tetra-phenyl-porphyrin-tetra-sulfonate (TPPS4), tetra-phenyl-chlorin-tetra-carboxylate (TPCC4), and chlorin e6 (Ce6)||Rheumatic disorders||Rapidly taken up (4 h) by the macrophages and accumulated in their cytoplasm and organelles||Schmitt et al. (2010)|
|PCEC nanoparticles in Pluronic hydrogels||Lidocaine||Local anesthesia||Produced long-lasting infiltration anaesthesia of about 360 min||Yin et al. (2009)|
|Poly(lactide-co-glycolic acid) and chitosan nanoparticle dispersed in HPMC and Carbopol gel||Spantide II||Allergic contact dermatitis and other skin inflammatory disorders||Nanogelinncreases potential for the percutaneous delivery of spantide II||Punit et al. (2012)|
|pH-sensitive polyvinyl pyrrolidone-poly (acrylic acid) (PVP/PAAc) nanogels||Pilocarpine||Maintain an adequate concentration of the pilocarpine at the site of action for prolonged period of time||Abd El-Rehim et al. (2013)|
|Cross-linked poly (ethylene glycol) and polyethylenimine||Oligonucleotides||Neurodegenerative diseases||Effectively transported across the BBB. The transport efficacy is further increased when the surface of the nanogel is modified with transferrin or insulin||Vinogradov et al. (2004)|
|Cholesterol bearing pullulan nanogels||Recombinant murine interleukine-12||Tumor immunotherapy||Sustained release nanogel||Farhana et al. (2013)|
|Poly(N-isopropylacrylamide) and chitosan||Hyperthermia cancer treatment and targeted drug delivery||Thermosensitive magnetically modalized||Farhana et al. (2013)|
|Cross-linked branched network of polyethyleneimine and PEG Polyplexnanogel||Fludarabine||Cancer||Elevated activity and reduced cytotoxicity||Farhana et al. (2013)|
|Biocompatible nanogel of cholesterol-bearing pullulan||As artificial chaperone||Treatment of Alzheimer’s disease||Inhibit aggregation of amyloid β-protein||Ikeda et al. (2006)|
|DNA nanogel with photo cross-linking||Genetic material||Gene therapy||Controlled delivery of plasmid DNA||Lee et al. (2009)|
|Carbopol/zinc oxide (ZnO) hybrid nanoparticle gel||ZnO nanoparticles||Antibacterial activity, bacterial inhibitor||Ismail et al. (2021)|
Table adapted from Swarnali et al., 2017