Nanostructure evolution under magnetic treatment

To investigate the mechanism of release, especially under stimulus, the nanostructural evolution of the SAIO@SiO₂ nanocarriers subjecting to HFMF were monitored, as shown in Fig. 7.7(a) and 7.7(b). Although the fast-response to the magnetic stimulus causing burst release was carried out under HFMF for a 4-min duration, the nanocarriers remained intact in structural integrity, indicating that the drug molecules, having a size less than 1 nm, have been accelerated considerably in passing across the silica shell. The rigid silica shell coated on the SAIO@SiO2

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Figure 7.7 TEM images of nanostructures of (a, b) SAIO@SiO2 nanocarriers, and (c) to (f) SAIO after 4-min duration of HFMF treatment. (a, b) SAIO@SiO2 nanocarriers displayed no obviously crack after HFMF treatment. (c-f) SAIO without silica shells showed obvious cracks or deformation after applying HFMF.

nanocarriers is acting like a framework to keep the integrity of the SAIO core phase from physical deformation or damage under extensive magnetic stimulus. After subjecting to HFMF treatment, Figure 7.7(b) displayed no observable cracks or defects developed on the thin silica shells when the IBU molecules was releasing.

In order to estimate the structural evolution of the core phase of the SAIO@SiO2

nanocarriers under the HFMF, the nanostructural evolution of SAIO core phase without the silica shells was examined. From TEM analysis, the morphological structure of the as-synthesized SAIO nanoparticles in the absence of HFMF treatment displayed excellent structural integrity, wherein the magnetic nanoparticles were well distributed with the PVA phase. However, after 4-min HFMF stimulus, the stresses induced by HFMF caused two types of structural deformation on the SAIO nanoparticles. First, nano-cavities of 20-60 nm in size were developed on the core

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SAIO nanoparticle, as shown in Figure 7.7(c) and (d), however, some nanoparticles seemingly remained structurally intact. Second, the stress–induced serious structural deformation of the SAIO nanoparticles exhibited in Figure 7.7(e) and (f). These nano-cavities are probably resulting from the dissolution of the PVA in aqueous solution under magnetic-induced heating. Because the HFMF is able to induce heat energy from the magnetic nanoparticles at a faster rate, some ―hot-spots‖ are believed to cause structural dissociation of the SAIO core, since it has well recognized that the heat generation, governed by the mechanism of magnetic energy dissipation for single-domain particles (Brown and Néel relaxations), is sensitive to the crystal size and the materials.^[28] The temperature of the solution (5 mg/cc water) will increase about 12 ^oC, from 24 ^oC to 34 ^oC. Once the energy induced by HFMF increased the temperature of SAIO nanoparticles, the PVA molecular chains became more flexible (glass transition temperature of PVA is about 80 ^oC), as they are subject to an aqueous and heating environment, causing the IBU molecules to diffuse more easily in the flexible and soft SAIO nanoparticles, whereupon a physical deformation of the SAIO nanoparticle was detected, as depicted in Figure 7.7(e) and 7.7(f).

To investigate the weight loss of PVA after HFMF stimulus, thermogravimetric analysis (TGA) was used. After 4-min period of HFMF treatment, as given in Table 7.1, the PVA lost 7% and 2% by weight for the SAIO nanoparticles (also as a core phase for the core-shell nanocarrier) and SAIO@SiO2 nanocarriers, respectively, indicating substantially large portion of the PVA phase still stayed within the core phase, especially for those covered with a silica shell. However, the findings suggest that the weight loss of the PVA in the core phase is a result of outward diffusion due to the presence of surface defects such as nanopores along the silica shell. This seems to provide a reasonable explanation of the burst-like release behavior. However, what is interestingly observed from the release behavior, Fig. 7.6(b), is that the release

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profile behaved as a near zero-order kinetic even under HFMF stimulus, which further substantiates that the regulating effect of the shell structure remained the same. In other words, while subjecting to the HFMF, the nanostructural perturbation of the inner core phase accelerated considerably the movement of the IBU molecules due to the dissociation of the PVA phase and in the meantime, thermally-induced diffusion, a significant increase in the collision frequency of the IBU to the silica shell by a factor of est. 10 was observed. In consequence, a burst-like release behavior for the SAIO@SiO2 nanocarrier was detected. However, once the stimulus was removed, the inner core phase must restore rapidly to original status, where the PVA solidified and thermal perturbation due to superparamagnetic nature of the nano-metric iron oxide nanoparticles ceased. The nanostructural integrity of the silica shell remained intact, where the regulating effect kept identically effective, as evidenced in the release profiles upon several ―on-off‖ operations, Figure 7.6(b).

Mechanical motion of iron oxide nanoparticles within the core phase under HFMF gives rise to an alternative contribution to the burst release pattern of the SAIO@SiO2 nanocarriers. The degree and speed of deformation of the SAIO core phase depended on the interactions among the nanomagnets and PVA phase, where both phases are intimately contact in a nanometric confinement. Magnetic nanoparticles in the magnetic field subject to stretch along the direction of the field due to the magnetostatic energy,

Ems = 1/2(N//-N┴)M²V (1)

where N// and N┴ are demagnetizing factors in the directions parallel and perpendicular to the magnetic field. E_ms is the energy of magnetic interaction of the magnetic moment M of the nanoparticles with magnetic field H. V is the volume of magnetic nanoparticles. While applying a magnetic field, magnetostatic interactions

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induced by magnetic field will cause an appearance of demagnetizing field inside the SAIO core. Owing to this magnetostatic interaction, the magnetic particles in the core phase will tend to move, resulting in establishing stresses inside the nanostructures.

Such stresses may act a factor accelerating the formation of the nano-cavities and deformation of SAIO nanoparticles as shown in Figure 7.7(c) to 7.7(f). From experimental observations, it suggests that such a HFMF-induced nanostructural evolution involves following four stages: (i) heating of the SAIO core locally, (ii) causing certain degree of relaxation of polyvinyl alcohol which further combines with (iii) the mechanical motions of iron oxide nanoparticles, following (iv) defect formation, which is especially pronounced for SAIO nanoparticles. Such a nanostructural evolution under HFMF stimulus surely enhances the burst release behavior from within the core phase for the SAIO@SiO2 nanocarriers.