Study on controlled drug permeation of magnetic-sensitive ferrogels:
Effect of Fe
3
O
4
and PVA
Ting-Yu Liu, Shang-Hsiu Hu, Kun-Ho Liu, Dean-Mo Liu, San-Yuan Chen
⁎
Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu, 300, Taiwan, ROC Received 29 June 2007; accepted 5 December 2007
Available online 15 December 2007
Abstract
A PVA-based magnetic-sensitive hydrogel (ferrogel) was fabricated by physical cross-linking through a freezing–thawing method. The influence of the constituting components, i.e., Fe3O4and PVA, on the magnetic-sensitive behavior of the ferrogels was systematically investigated
in terms of permeability coefficient (P), partition coefficient (H), space restriction and magnetization. The results show that, the P value in these ferrogels decreases and displays a magnetic sensitivity when it is subjected to magnetic field (MF), which is correlated with the change of H value. In addition, it was found that although the factor of space restriction or magnetization exerts opposite effect on resulting magnetic-sensitive behavior, the superior magnetic-sensitive behavior was observed for the ferrogels with an optimal composition of 17–34% Fe3O4and 10–12.5%
PVA, and can be well correlated with theoretical calculation from the critical parameters of available free volume per nanoparticle (Vfree) and
magnetization. A map of magnetic-sensitive behavior was constructed, where a region with relatively stable and highly stimuli-responsive behavior in terms of the concentration of Fe3O4was observed, however, below or above the“saturation” region (17–34% Fe3O4), a reduction in
the magnetic-sensitive behavior was detected. The resulting ferrogels can be engineered with a precise control of the opening and closure of pore configuration, which allows a burst release or no-release action of therapeutically active agent to be controlled externally and magnetically. This suggests that this type of ferrogel can be considered as a class of novel magnetically-tunable drug delivery system.
© 2007 Elsevier B.V. All rights reserved.
Keywords: PVA; Fe3O4nanoparticles; Magnetic hydrogel (ferrogel); Controlled permeation
1. Introduction
Certain polymer gels represent one class of actuators that have the unique ability to change elastic and swelling properties in a reversible manner. Volumetric phase transition in response to an infinitesimal change of external stimuli, such as pH, temperature, electric and magnetic field (MF) in various hydrogels has been observed[1–10]. In order to accelerate the response of an adaptive hydrogel to stimuli, a magnetic-sensitive hydrogel (ferrogel) has been developed. A ferrogel is a physical (or chemical) cross-linked polymer network containing mag-netic particles. Magmag-netic-field sensitive gels are unique materials
in that they are mechanically soft and highly elastic and at the same time they exhibit a strong magnetic response.
The principle of shape deformation and motility of ferrogels in response to drug release is based on their unique magnetic-elastic behavior. Gel motions are driven and controlled by MF and the final shape is determined by a balance of magnetic and elastic interaction [11]. Recently, some magnetic-stimuli in response to drug delivery have been applied in clinical therapy. For example, the polyelectrolyte microcapsules embedded with Co/Au nanoparticles could increase its permeability (P) to macromolecules like FITC-labeled dextran by alternating current (AC) magnetic switch[12]. Saslawski et al. reported the gelatin microsphere that was cross-linked by polyethyleni-mine for the pulsed delivery of insulin by oscillating MF[13]. However, little investigation has been reported on controlled permeation of drugs under the direct current (DC) MF through the controlled deformation of ferrogels upon a simple“on” and
Journal of Controlled Release 126 (2008) 228–236
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⁎ Corresponding author. Tel.: +886 3 5731818; fax: +886 3 5725490. E-mail address:[email protected](S.-Y. Chen). 0168-3659/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2007.12.006
“off” switch mode. In our previous work, the bursting and magnetic-sensitive behaviors of PVA-based ferrogels were investigated with various particle sizes of Fe3O4and switching
duration time of magnetic fields [14]. From our previous experimental observation, it was found that permeation rate of vitamin B12, as a model molecule, decreased with the increased
intensity of direct current (DC) magnetic field. This induces the Fe3O4 particles within the ferrogel to aggregate together
instantly, leading to a rapid decrease in the porosity of the ferrogel, where the ferrogel was characterized as a “close” configuration[14,15]. In other words, while the imposed field induces magnetic dipoles, mutual particle interactions occur if the particles are so closely packed that the local field can influence their neighbors. The particles attract with each other when aligned in an end-to-end configuration and thus a“pearl– chain structure” was developed[16]. Therefore, the drugs are restrictedly confined in the network of the ferrogels, causing a rapid and significant reduction in the diffusion of the drug from the ferrogel, due to the attractive forces that reduced the pore size of the ferrogel. While turning off the field, the pores in the ferrogel re-open instantly, the drug release turned back to normal diffusion profile.
The above-mentioned phenomenon indicates that the optimal magnetic-sensitive behavior of the ferrogel was not only dependent on the particle size of Fe3O4but also on the
constituting components, i.e., Fe3O4and PVA. Therefore, the
influence of the respective constituting components of the ferrogels on magnetic-sensitive behavior and partition coeffi-cient (H ) will be systematically investigated in this work. These magnetic-sensitive behaviors will be further correlated with theoretical calculation of both space restriction and magnetization. According to the proposed model, an optimal scenario from both experimental findings and calculations would be deduced to fabricate a ferrogel with controlled smart configuration.
2. Materials and methods 2.1. Ferrogel preparation
A freezing–thawing technique was used to prepare the ferrogel [17]. In our experience, the physical-cross-linked ferrogel by a freezing–thawing technique was used in the present study because it presents more elastic and soft properties than that fabricated by chemical-cross-linking. First, various weight/volume (w/v)% of polyvinyl alcohol (PVA, Fluka, M.W.: 72,000, degree of hydrolysation: 97.5– 99.5 mol%) was dissolved in 10 ml dimethylsulfoxide (DMSO) at 80 °C under stirring for 6h, and then mixed with various (w/v)% of magnetic particles at 60 °C under ultrasonication for 6h to ensure that the magnetic particles (diameter ca. 150–500 nm, Aldrich) can be well-dispersed, as shown inTable 1. The resulting solution was then poured into plastic dish and kept frozen at−20 °C for 16 h. Subsequently, the gels were thawed at 25 °C for 5 h. This cyclic process including freezing and thawing was repeated for 5 times. Finally, prior to the release test, the ferrogels were washed five
times and then immersed in the water for 24 h to completely remove DMSO.
2.2. Diffusion characterizations
The diffusion coefficients of the solutes were measured under switching MF (magnetic strength of about 400 Oe mea-sured by Gauss meter) in a diffusion diaphragm cell (side-by-side cell) [14]. The solution in the donor side is 80 ml of isotonic phosphate buffer (PBS) (pH 7.4) containing 200 ppm of the model drug (vitamin B12). The receptor compartment,
separated by the ferrogel, was filled with 80 ml of PBS solution. The concentration of each compound in the receptor compart-ment was determined at λ=361 nm using a UV spectro-photometer. The permeation coefficient (P, cm2/min) was calculated according to the following equation for the diaphragm cell: ln Cd0 Cd Cr ¼2 DH½ At dV ; P ¼ DHð Þ ð1Þ where Cd0 is the initial concentration of the permeant in the
donor compartment; Cdand Crare indicative of the
concentra-tions in the donor side and receptor side, respectively; D is the diffusion coefficient (cm2/min) [18–21]; H is the partition coefficient; A is the effective area of the ferrogel; δ is the thickness of the ferrogel; V are respectively the volumes of solution in the donor and receptor compartment (both are 80 ml). By plotting ln[Cd0/(Cd−Cr)] versus time (t), the
per-meability coefficient (P) can be calculated from the slope of the line by Eq. (1). Each data point was obtained by averaging of at least three measurements.
Moreover, the dry weight (Wdry) of drug-free ferrogel was
immersed in the release medium until equilibrium state and then the wet weight (Wwet) was recorded. Subsequently, the ferrogel
was immersed in 10 ml of vitamin B12-containing medium.
Table 1
Average permeability coefficient (P) of the ferrogels at a given magnetic field Ferrogels PVA (w/v)%a Fe3O4 (w/v)%a PONb POFFc ΔPOFF–ONd Pure PVA10 10 – 54 ± 3 54 ± 5 0 PVA10-MP3.75 10 3.75 123 ± 6 172 ± 9 49 PVA10-MP8.5 10 8.5 86 ± 9 170 ± 5 84 PVA10-MP17 10 17 54 ± 9 161 ± 12 107 PVA10-MP25.5 10 25.5 43 ± 11 154 ± 5 111 PVA10-MP34 10 34 31 ± 5 141 ± 7 110 PVA10-MP51 10 51 40 ± 8 131 ± 9 91 PVA10-MP68 10 68 45 ± 6 117 ± 5 72
a (w/v)% means the weight/volume percentage (weight of PVA or Fe 3O4
particles/volume of DMSO (v)), ex. 1 g of PVA and 10 ml of DMSO is 10 (w/v)% of the column of PVA (w/v)%.
b Average permeability coefficient (10− 6 cm2/min) at magnetic fields
switching“on” (MF ON) (n=3).
c
Average permeability coefficient (10− 6 cm2/min) at magnetic fields switching“off” (MF OFF) (n=3).
d
Magnetic-sensitive behaviors: average permeability coefficient (10− 6cm2/min) at MF OFF−average permeability coefficient (10− 6cm2/min) at MF ON. (n = 3).
Partition coefficient (H ) was determined from the initial (C0)
and equilibrium (Ce) concentrations of vitamin B12-containing
mediums by Eq. (2)[20,21]. H¼WdryðC0 CeÞ
WwetCe
ð2Þ 2.3. Porosity determination[19]
The porosity of the ferrogels was determined by measuring the true density and the bulk density. To measure the true density, a freeze-dried ferrogels were placed in a vacuum oven and the weight of the sample was measured (M). Afterwards, the ferrogels were put into the cell chamber cup of a pyconometer (Micromeritics, 1305) to measure the true volume (Vt). The true
density (ρt) was then calculated according to Eq. (3). To
measure the bulk density, ferrogels were vacuum dried and then the area was measured. The thickness of the ferrogels was measured ten times with a digital gauge meter (Mitutoyo IDF-112) to obtain the bulk volume (Vb). The bulk density (ρb) was
then calculated according to Eq. (4). The porosity (ε) of the ferrogels was calculated according to Eq. (5).
qt¼ M=Vt ð3Þ
qb¼ M=Vb ð4Þ
e ¼ Vbulk=Vtrue 1 ð5Þ
3. Results and discussion 3.1. Role of iron oxide content
According to our pervious study[14], it was found that the larger magnetic particles exhibited better magnetic-sensitive behaviors. Therefore, magnetic particles with size between 150 and 500 nm were employed in the present investigation.Table 1
gives a series of resulting average P values of the ferrogels with a number of Fe3O4concentrations at a given amount of PVA
concentration. The influence of Fe3O4 concentration is then
constructed into Fig. 1(a) with respect to a corresponding change of the P value upon on–off operation of the MF.
As shown inFig. 1(a), as the Fe3O4nanoparticles were added
into the PVA, the P value was much increased compared to that of pure PVA. It was found that the P value in the ferrogel membrane with only 3.75 w/v% Fe3O4 is more than 3 times
permeable to vitamin B12than that of pure PVA in the absence
of MF. However, with the increase of Fe3O4addition, the P
value decreased linearly and slowly with Fe3O4concentration in
the absence of magnetic fields (POFF). In contrast, the drug
permeation in the presence of magnetic fields (PON) decreased
Fig. 1. (a) Both permeability coefficient (P) and partition coefficient (H ) of ferrogels in “on” or “off” mode of a given magnetic field; (b) Diffusion coefficient (D) of ferrogels in“on” or “off” mode of a given magnetic field.; (c) Magnetic-sensitive behaviors of ferrogels with different Fe3O4
concentra-tion; Region A: region of increasing“sensitivity”; Region B: saturation region; Region C: region of decreasing“sensitivity”.
rapidly with Fe3O4 up to 34%, then, increased slightly with
further increase to 68%. A plethora of Fe3O4(51% and 68%)
added in the PVA hydrogel caused a phase separation of PVA to form broken pores; PONthus increased slightly in the later half.
It was believed that there exists a relationship between the P and H value of the drug inside the membrane (see Eq. (1), where P = DH). As illustrated inFig. 1(a), when a smaller amount of 3.75 w/v% Fe3O4particles was added into PVA (ex.
PVA10-MP3.75), it caused a considerable increase (2.3 times) in the H value (0.125) compared to that (0.055) in the pure PVA hydrogel. It is then suggested that the addition of iron oxide nanoparticles in the membrane may induce higher porosity to promote the ability of drug absorption of the ferrogel. However, it was observed that the H value decreased with increasing Fe3O4contents. Especially in the presence of MF, the decrease
in the H value becomes more remarkable compared to that in the absence of MF. The decreased H value in the presence of MF is probably related to the shrunk volume of ferrogels induced by Fe3O4nanoparticles aggregation to further decrease
the pore size and porosity. From above-mentioned results, it can be inferred that the magnetic-sensitive behaviors, i.e., the difference in the P value between MF“on” and “off” modes were primarily affected by the change of H and D value, especially D value (for the concentration of 34%,ΔPOFF–ON/
POFF= 110/141 = 0.78, whereas ΔHOFF–ON/ HOFF= 0.01/
0.11 = 0.09). The influence of Fe3O4 concentration value on
the corresponding change of D value is then constructed into
Fig. 1(b) upon on–off operation of the MF (DONand DOFF). It
could be found that the D curves show similar trend to the P ones. The D value decreased slightly with Fe3O4concentration
in the DON, but decreased rapidly with Fe3O4up to 34%, then,
increased slightly with further increase to 68% in the DOFF. A
plateau of magnetic-sensitive behavior (Dwithout MF−Dwith MF)
was found in the range of 17 and 34% Fe3O4. It means that the
drug inner the ferrogel was obstructed more strongly in this range, rather than the others, ex. 8–17% and 34–68%. This indicates that the diffusion coefficient (D) plays a rather important role to evaluate the behavior of drug inner the ferrogel.
In addition, as shown in a magnetic-sensitive behavior map of Fig. 1(c), it showed an increase with Fe3O4 until 17%,
indicating the region of increasing sensitivity (Region A). Subsequently, a plateau profile is reached while Fe3O4is lying
between 17 and 34%, indicating the magnetic-sensitive behavior reaching a saturation region (Region B). However, the magnetic-sensitive behaviors decreased with further addi-tion of Fe3O4 up to 68% (Region C), indicating a decreased
sensitivity to a given magnetic stimulation. These results indicated that the best magnetic-sensitive behaviors occur for the 10% PVA-ferrogels with 17–34% Fe3O4concentration.
3.1.1. Effects of space restriction
The reason for such a dependence of Fe3O4concentration
on the evolution of the magnetic-sensitive map may be ac-countable for as a result of space restriction and magnetization. In Fig. 2(a), a model with a fixed volume of the unit cell is adapted for schematically illustrating the spatial arrangement
of the magnetic particles (presumed to be uniformly distrib-uted) in the ferrogels (namely PVA10-MP17, PVA10-MP34 and PVA10-MP68). Here, the SEM cross-sectional image of the PVA10-MP17, PVA10-MP34, and PVA10-MP68 ferrogels,
Fig. 2(b), in corresponding to model inFig. 2(a) shows that the magnetic particles are well-dispersed in the PVA hydrogel, and it seems to be intertwined with Fe3O4particles. The volume
fraction, Vf(Fe3O4) of Fe3O4particles in the ferrogel and the
number of Fe3O4particles for unit volume of the ferrogel (No.
Fe3O4) in the unit cell can be calculated as follows:
VfðFe3O4Þ ¼ WFe3O4=qFe3O4 Vferrogel 100k v=v%ð Þ ð6Þ No: Feð 3O4Þ ¼ VfðFe3O4Þ 4=3pr3 ð7Þ
where ρFe3O4 is the density of Fe3O4 particles (5.2 g/cm3);
WFe3O4means the total addition weight of the Fe3O4particles
in the ferrogel. Therefore, WFe3O4/ρFe3O4= VFe3O4 represents
the total volume of Fe3O4in the ferrogel. 4/3πr3indicates the
volume of a Fe3O4 particle if the particle is assumed to be
spherical. The total number of the Fe3O4particles is VFe3O4/4/
3πr3
where r is the radius of the iron oxide particle and is assumed to have an average diameter of 250 nm, i.e., r = 125 nm. For the PVA10-MP17 ferrogel, there are 17.1 Fe3O4particles in
the unit cell (1μm3), 33.3 Fe3O4particles in the PVA10-MP34
ferrogel, and 58.7 Fe3O4particles in the PVA10-BM68 ferrogel,
which are schematically shown in the Fig. 2(a). In order to conveniently and clearly express the relative number of the Fe3O4
particles in a basic unit cell, a model unit cell with a volume of 600 nm3was used, as displayed inFig. 2(a), and there are ca. 3.69 Fe3O4particles in the given volume of the model cell for
PVA10-MP17 ferrogel, 7.19 and 12.69 Fe3O4particles for PVA10-MP34
and PVA10-MP68 ferrogels, respectively. Furthermore, VFerrogel
represents the bulk volume of the ferrogel determined by the length, width, and thickness of various ferrogels.
In addition, the average porosity (%) of these ferrogels can be measured by a pyconometer and calculated by Eqs. (3)–(5), where the porosity in the ferrogel decreased with increasing Fe3O4, as illustrated inFig. 3(a). This indicates that increase in
the concentration of Fe3O4caused a reduction of porosity, and
the lower porosity will slower the permeation rate of the model drug in the absence of MF, i.e., MF “OFF”. Moreover, it was found that the porosity of the ferrogel decreases linearly with the volume fraction occupied by iron oxide. The variation of those two parameters can be fitted by following equation: Porosityð Þ þ Vk fðFe3O4Þ v=v%ð Þ þ x ¼ 100k
where x = 33.6 (+/−1.8) % may be interpreted as the volume fraction of organic matrix (i.e. PVA, and DMSO).
Although greater amount of Fe3O4particles can increase the
magnetization of the ferrogel, the space available for the Fe3O4
particles to freely move (where the available free volume per nanoparticle (Vfree) was defined as below) will correspondingly
the Fe3O4particles is too small, it will inhibit the movement of
the Fe3O4particles in the unit cell, thus, the magnetic-sensitive
behavior will decrease even though those particles exhibited high magnetization (Ms).
The available free volume of each magnetic nanoparticle can be calculated by Eq. (8):
Available free volume per nanoparticle Vð freeÞ ¼Porosityð Þ Vk ferrogel
No: Feð 3O4Þ
ð8Þ As given in Fig. 3(b), Vfree is decreased in a
power-law-dependent manner with increasing Fe3O4concentration. Vfreein
the PVA10-MP3.75 ferrogel (33.88 μm3) is about 30 times
higher than that in the PVA10-MP68 ferrogel (0.95 μm3), calculated by Eq. (8).
3.1.2. Effects of magnetization
In regard to the magnetization of the Fe3O4in the ferrogels,
the interaction energy (Eint) between two particles with
identical moment magnetization (Ms) can be given as follows
[22–23]: Eint∝
Ms2ð3cosw1cosw2 cosaÞ
d3 ð9Þ
where δ (μm) is the center-to-center distance between two neighboring particles, which is calculated by d + 2r; r is the
Fig. 2. (a) Models of the unit cell (600 nm2) of PVA-based ferrogels which Fe
3O4particles distributed; (b) SEM cross-section image of PVA10-MP34 ferrogel.
average radius of Fe3O4 particles (ca. 125 nm); d is the
surface-to-surface distance between two neighboring particles; ψ1 and ψ2 are the angles between δ and two moments,
re-spectively;α is the angle between the two moments. However, d is hardly precisely measured. Therefore, a rough measure-ment was performed by SEM as observed in Fig. 2(b). For example, the average d value in the PVA10-MP34 ferrogel was about 1μm that is approximately the same order of magnitude to that (0.75 μm) calculated from the following presumed model (see Fig. 2(c) and Eq. (10)). From the schematic drawing, it can be found that Vfreeis equal to43p ðdþ rÞ
3 r3 h i : Therefore, d¼ 3 4pVfreeþ r 3 1=3 r ð10Þ
Therefore, the average distance (d ) between particles will be used in this work to evaluate the Eint. The Ms of various
ferrogels was measured by a vibrating sample magnetometer (VSM, Toei VSM-5, USA). The Ms increased with the Fe3O4
addition, as illustrated by the magnetization curves in Fig. 4. Further, (3cosψ1cosψ2−cosα.) and other interrelated factors
were hypothesized as constant (ϕ). Hence, to combine Eq. (9) with Eq. (10), the interaction energy (Eint) can be well
char-acterized using Eq. (11)
Eint¼ Ms2 dþ 2r
ð Þ3/ ð11Þ
The Eint–Fe3O4concentration correlation, shown inFig. 3(b),
shows that the interaction energy is increased, followed by a power-law dependence, with increasing Fe3O4
concentra-tion. The interaction energy in the PVA10-MP68 ferrogel (865.68 emu2/μm3×ϕ) is about 3150 times higher than that in the PVA10-MP3.75 ferrogel (0.27 emu2/μm3×ϕ), as shown in
Fig. 3(b).
Based on these calculations, it is clearly demonstrated that the lower Fe3O4 concentration leaves larger Vfreebut poorer
interaction energy between the particles in the ferrogels, and vice versa, for the ferrogels with higher Fe3O4concentration.
Therefore, the “optimal” magnetic-sensitive behavior is virtually interplaying between the Vfree and the interaction
energy in the ferrogels. The concentration of the Fe3O4for the
optimal balance between the two factors can be obtained from the intersection of two power-law-dependent curves inFig. 3
(b), where an amount of between 30 and 34% of the Fe3O4was
derived. This concentration range is exactly located within the saturation region of the magnetic sensitivity map (Region B) shown inFig. 1(c). It can be anticipated that the ferrogels with Fe3O4 concentration in the range of 30–34% offer the best
spatial configuration of the particles in the unit cell model facilitating both Vfree and magnetization. By translating to
what experimentally observed, the PVA10-MP34 ferrogel does display the optimal “opening-&-closure” configuration with respect to“on–off” MF operation and also illustrated the best magnetic-sensitive behavior, as evidenced inFig. 1(a). In other words, the magnetic particles distributed in the PVA10-BM34 ferrogel presents the best spatial configuration for optimizing both Vfree and magnetization among the other
compositions.
Fig. 4. Hysteresis loop analysis of the ferrogels incorporated with various Fe3O4
additions measured by VSM.
Fig. 3. Comparison of (a) porosity (%), volume fraction of Fe3O4particles
(Vf(Fe2O4) and magnetization (Ms); (b) both available free volume per
nanoparticle (Vfree) and interaction energy (Eint) of ferrogels dependence of
3.2. Role of PVA content
Since the “closure” and “opening” configurations of the ferrogels are dependent solely on the operating mechanism of both magnetic particles and the polymeric phase, i.e., PVA, under the action (ON mode) and removal (OFF mode) of the magnetic field. The polymeric phase is virtually a passive phase
that intimately associated with the movement of magnetizing or de-magnetizing Fe3O4nanoparticles in the ferrogel. However,
PVA addition reduced the porosity and formed more rigid ferrogels and thus, the drug permeation rate, corresponding to P value, will surely reduce under on–off operation of the magnetic field. Thus, the change in the concentration of the polymeric phase in the ferrogels will affect its ability to ef-fectively enclose and release an active ingredient from the ferrogels under a fixed amount of Fe3O4 concentration in a
given strength of magnetic field. To elucidate the influence of the PVA on the magnetic-sensitive behavior in the ferrogels, PVA concentrations of 5%, 7.5%, 10%, and 12.5% were se-lected for the ferrogels with 17% and 34% Fe3O4nanoparticles
(hereinafter termed 17% and 34% Fe3O4 ferrogels), which
has been shown in Fig. 1(b) to exhibit stable and excellent magnetic-sensitive behavior (Region B).
Fig. 5(a) and (b) shows the variation of P value of the ferrogels before (i.e., MF“OFF”, POFF) and after (MF“ON”,
PON) an MF operation. For 17% Fe3O4ferrogel, that the value
of POFF decreased sharply with increasing PVA concentration
[seeFig. 5(a)], but PONdecreased slowly with PVA
concentra-tion. In addition, the change in the P value with respect to the PVA concentration for 34% Fe3O4 ferrogels exhibits similar
trend before (MF“OFF”), and after (MF “ON”) magnetization. However, compared with 17% Fe3O4 ferrogels, PON of 34%
Fe3O4ferrogels decreased slightly (followed by a power-law
dependence) with the increased PVA concentration, inFig. 5(b). It displays a“saturation” region while increasing PVA over the range of 10–12.5%, implying that the best “closure” config-uration in this system is lying between 10 and 12.5% PVA content. According to these findings, it can be found that the magnetic sensitivity is decreased considerably and linearly with increasing PVA concentration for the 17% Fe3O4ferrogels but
decreased relatively slowly for the 34% Fe3O4 ferrogels as
shown inFig. 5(c), indicating that the magnetic-sensitive be-havior of the ferrogels is proportionally decreased by the addition of PVA. However, the effect of PVA appears to be less pronounced in the 34% Fe3O4 ferrogel, since its magnetic
Fig. 6. Correlation of both available free volume per nanoparticle (Vfree) and
interaction energy (Eint) in the ferrogels between 17% Fe3O4and 34% Fe3O4
contents. Fig. 5. Permeability coefficient of various PVA addition in“on” or “off” mode of
a given magnetic field with (a) 17% Fe3O4contents and (b) 34% Fe3O4contents;
(c) Comparison of magnetic-sensitive behaviors between 17% and 34% Fe3O4
behavior does not display remarkable fluctuation or change with increasing PVA as compared to that with 17% Fe3O4ferrogel.
The above-mentioned results can be further explained in terms of the effect of space restriction and magnetization, as illustrated in Fig. 6 for 17% and 34% Fe3O4 ferrogels,
respectively. PVA addition in both ferrogels (i.e., 17% and 34% Fe3O4) leads to a reduction in both Vfree(calculated using
Eq. (8)) and the interaction energy (Eint). Consequently, P value
under MF“OFF” is decreased sharply. In the meantime, it also reveals a reduction in the permeation rate of the drug from the ferrogels with increasing PVA under MF“ON” operation due to lower porosity, and these have been experimentally supported in
Fig. 5(a) and (b). It is evidenced that increasing PVA not only reduces Vfree but also weakens Eint of the magnetic particles
in the ferrogels. Therefore, both Vfree and Eint are decreased
linearly with PVA concentration.
In addition, 17 wt.% series ferrogel exhibited better magnetic sensitivity in the lower concentration region of PVA (ex. 5 wt.% PVA) compared to 34 wt.% series ferrogel, because the Vfreeof
17 wt.% (7.3μm3) is larger than that of 34 wt.% (3.1μm3), as shown inFig. 6. It means that iron oxide is easier to move in the 17 wt.% series ferrogel than that in the 34 wt.% series. How-ever, the interaction energy (Eint) of 17 wt.% series ferrogel
(15.6 emu2/μm3ϕ) is much smaller than that of 34% series (224.8 emu2/μm3ϕ). Therefore, Eintvalue in the 17 wt.% series
might be not large enough for magnetic sensitivity with higher PVA addition, which is the reason that the magnetic sensitivity decreased so sharply in the 17 wt.% series. In contrast, 34 wt.% series ferrogel displays smaller Vfree but higher Eint, which
means that they exhibit a higher Eintbut limited Vfree. That is
why the magnetic sensitivity of 34 wt.% series is higher than 17 wt.% series (higher Eint and lower Vfree), although both
factors of 17 wt.% and 34 wt.% series were decreased with increasing PVA.
Moreover, as compared to Fig. 3(b) with an increase of Fe3O4, Eintincreased but Vfree decreased, it is clear to realize
that both the Fe3O4and PVA constituents play different roles for
drug permeation behavior and magnetic-sensitive behavior of the resulting ferrogels. Accordingly, the resulting ferrogels can be manipulated externally and magnetically with a precise control of the opening and closure of pore configuration within the network structure of the ferrogels.
4. Concluding remarks
The effect of the Fe3O4and matrix PVA on the
magnetic-sensitive behavior of ferrogels was systematically investigated. Magnetic-sensitive behavior map in terms of Fe3O4
concentra-tion was constructed and the behavior reached a“saturation” region in the range of 17–34% Fe3O4. Below or above that
region, a reduction in the magnetic-sensitive behavior was observed. Both the concentration dependence of the magnetic-sensitive behavior with respect to PVA and Fe3O4 can be
explainable in terms of a space restriction model (translated into available free volume) and magnetization (translated into the interaction energy). These two factors impose opposite effect to the resulting magnetic-sensitive behavior, and accordingly, an
optimal combination of both available free volume and inter-action energy can be found for the ferrogels with a composition of 17–34% Fe3O4and 10–12.5% PVA. It is anticipated that the
ferrogels with an optimal mixture of PVA and Fe3O4display a
magnetic-sensitive behavior that permits the ferrogels techno-logically applicable as a microdevice for delivery of therapeutic drugs in a highly controllable manner.
Acknowledgement
The authors gratefully acknowledge the National Science Council of the Republic of China for its financial support through Contract No. NSC-95-2221-E-009-126.
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