SMART NANOMATERIALS *
CHAPTER 3 CHAPTER 3
3.4 SYNTHESIS
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An example of using enzymes as external stimulus is the experiment done by Jin et al. (Fig. 3.6), where a copolymer made of phenyboronic acid and sugar-based side chains was loaded with insulin.
Once free glucose was added, it competed to bind with the boronic acid within the polymer, breaking the cross-links and inducing swelling of the nanoparticle, therefore releasing its payload of insulin.
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polymerization methods. Below is a detailed discussion of some of the most used synthesis methods of smart nanoparticles. Other examples commonly encountered are as follows:
a. Adsorption of polymers on nanoparticles: This is the oldest and simplest method for the
fabrication of responsive nanoparticles, where a polymer is adsorbed on the surface of the particle and regulates interactions in the colloidal suspension due to a range of different effects (steric, electrostatic, bridging, and depletion mechanisms).
b. Self-assembly of micelles and polymersomes from amphiphilic block copolymers: In this method, block copolymers form various types of self-assembled structures from micelles to continuous bilayers (depending on solvent selectivity). This solvent compatibility results in swelling and packing of particles. Common physical changes within particle are in the aggregate size. Changes to aggregate architecture, structure and responsiveness to pH, ionic strength, thermal, and redox stimuli are among those most commonly considered. Unique examples of stimuli are osmotic shock, shear flow, ionic exchange, etc.
3.4.1 COACERVATION/PRECIPITATION
Polymer solutions undergo a liquid–liquid phase separation where the polymer-rich phase is referred to as the coacervate phase. Dispersion of formed colloids is unstable and there is a tendency for coa- lescence (merging of colloids). However, synthesis allows control of droplet size (either by chemical cross-linking or physical gelation). It is subdivided into simple and complex precipitation. Simple coacervation is often used for entrapping drugs into microcapsules (due to reversibility of process of forming particles), whereas complex coacervation yields particles with two or more stimuli responses.
These complex particles are also called “iontropic” hydrogels (Motomov et al., 2010). Another advan- tage of fabricating using these methods is that particles can be prepared under mild conditions without using organic solvents, surfactants, or steric stabilizers.
Fig. 3.7 shows an example of a pH-responsive nanoparticle prepared by polymerizing an acrylic acid monomer in the presence of gelatin instead of chitosan (Zhang, Wang, Wang, Zhao, & Wu, 2007).
FIGURE 3.7
Schematic of the formation of poly(acrylic acid) (pAA)-gelatin complex coacervate particles and their ph- triggered swelling transition.
From Zhang, Y. W., Wang, Z., Wang, Y., Zhao, H., & Wu, C. (2007). Facile preparation of pH-responsive gelatin-based-core-shell polymeric nanoparticles at high concentrations via template polymerization. Polymer, 5639–5645.
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The chemical cross-linking of gelatin with PAA produced a chemically stable complex particle.
A surface enriched particle with gelatin chains contributed to colloidal stability, and the swelling/
shrinking due to change in pH affected the volume by a factor of 80 (Zhang et al., 2007). Another way of using this process is production from precipitation on templates. This occurs when a solid or poly- mer particles are present in a solution in which the coacervation process and the polymer-rich phase deposits on the particle surface producing core–shell particles. This phenomenon is also referred to as surface-controlled precipitation and hetero-coagulation of polymers on colloidal particles.
This method allows preparing relatively thick, microscopically homogeneous coatings in a single or a few steps from either charged or noncharged polymers (Radtchenko, Sukhorukov, & Mohwald, 2007). Branches of this process are core–shell and micelle-like particles by complex coacervation, and Micelle-like particles from polyelectrolyte–ionic surfactant complexes.
3.4.2 LAYER-BY-LAYER POLYMERIC SHELL
This is a method of deposition of oppositely charged species (such as organic molecules, proteins, polyelectrolytes, etc.) and was pioneered by Iler (1966) and later studied by Decher Fendler (1997) and Lvov et al. (1995).
It was successfully applied for the fabrication of polymer shells around particulate cores and trans- formation of the core–shell particles into hollow spheres with layer-by-layer gel walls. An example of this synthesis is the formation of capsules (Fig. 3.8), process design by Donath et al., where a stepwise
FIGURE 3.8
(A–f) Schematics of pE deposition process and subsequent core decomposition. (G) SEM image of nine- layer [(pSS/pAh)4/pSS] pE shells after solubilization of the Mf core. pE, polyelectrolites; pSS, poly(sodium styrenesulfonate); pAh, poly(allylamine hydrochloride); Mf, melamine formaldehyde.
From Donath, E., Sukhorukov, G.B., Caruso, F., Davis, S.A., Helmuth Möhwald, H. (1998). Novel hollow polymer shells by colloid- templated assembly of polyelectrolytes. Angewandte Chemie International Edition.
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adsorption was performed of oppositely charged polyelectrolytes onto melanin resin templates (later dissolved in acid).
Steps (A–D) represent the stepwise film formation by repeated exposure of the colloids to poly- electrolytes of alternating charge. The excess polyelectrolyte was removed by cycles of centrifugation and washing before the next layer is deposited. Step (E) was performed after the desired amount of coatings was deposited and the particle was exposed to 0.1 M HCl and the core decomposed immedi- ately. Finally, (F) represents the suspension of free polyelectrolyte hollow shells, poly(sodium styrene sulfonate). By combining weak polyelectrolytes and thermoresponsive polymers in the layer-by-layer shell, a nanoparticle with dual pH and thermoresponsive properties can also be produced (Wang, Cui, Duan, & Yang, 2002).
3.4.3 GRAFTING ONTO THE SURFACE OF PARTICLES
Techniques imply chemical attachment of functional polymers, brushes which are a collection of densely packed polymer chains that provides the particle responsiveness to stimuli. These are normally attached to the core surface by physisorption or covalent chemical attachment (Motomov et al., 2010).
Grafting techniques provide nanoparticles sensitive to many stimuli (i.e., changes in solvent quality, pH, ionic strength, temperature).
“Grafting-to” and “grafting-from” are two major approaches. “Grafting-to” is a method that involves a chemical reaction between the presynthesized/end-functionalized polymer brushes and particle sur- face modified by complementary functional groups. It has advantages such as its simplicity, robustness, and the use of well-characterized polymers (Motomov et al., 2010). Resultant brushes are of moderate grafting density (due to diffusion kinetics of end-functionalized polymer chains) and lead to low film thickness due to excluded volume effects imparted by previously adsorbed polymer chains.
The “grafting-from” method overcomes the limitations of the grafting-to approach, yielding densely packed polymer brushes through surface initiated polymerization. This surface is compatible with a wide range of polymerization chemistries, including anionic, cationic, plasma induced, condensa- tion, photochemical, electrochemical, controlled radical polymerization, and ring-opening metathesis polymerization (Motomov et al., 2010). In the production of “smart” gold nanoparticles (Li, He, &
Li, 2009), an initiator immobilized on the surface of gold nanoparticles provides controlled polymer molecular weight, narrow distribution of brushes, and regular shell thickness. Layers of high grafting densities are also produced because the active centers (radicals, ions, and ion pairs) of the growing chains are easily accessible for monomer molecules in the swollen brush in the course of polymeriza- tion. A simplified schematic of the difference in synthesis on gold nanoparticles is shown in Fig. 3.9.
3.4.4 HETEROGENEOUS POLYMERIZATION
Many techniques have been developed and have numerous applications for synthesizing monodisperse core–shell particles. Some of the most used synthetic approaches for preparation of “smart” nanoparti- cles are emulsion, precipitation, and dispersion polymerizations (Pichot, Elaissari, Duracher, Meunier,
& Sauzedde, 2001; Pichot, 2004). The main steps of these methods are nucleation and growth.
An advantage is that polymerization allows for synthesis of hybrid particles (organic and inorganic materials—i.e., silica, alumina, iron oxide, and noble metal) allowing for design and production of temperature, pH, ionic strength, and UV-responsive particles. Berndt et al. (Fig. 3.10) synthesized a
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FIGURE 3.10
Radial density profiles for the temperature-sensitive core–shell microgel particles at 25, 39, and 50°c; core (red) (shaded gray in print version), shell (blue) (dark gray in print version), the black dotted lines show the total density.
From Berndt, I., Pedersen, J. S., & Richtering, W. (2006), Temperature-sensitive core–shell microgel particles with dense shell.
Angewandte Chemie International Edition, 45, 1737–1741.
FIGURE 3.9
Simple schematic for producing gold–polymer nanoparticles.
From Li, D., He, Q., & Li, J. (2009). Smart core/shell nanocomposites: intelligent polymers modified gold nanoparticles. Advances in Colloid and Interface Science, 28–38.
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