Preparation and Properties of Monodisperse pH-Responsive Microgels
7.4 Monodisperse Cationic pH-Responsive Hydrogel Capsules
7.4 Monodisperse Cationic pH-Responsive Hydrogel Capsules 163
Fig. 7.9 Optical micrographs of PDM microgels prepared with 10 wt % of PVP K30 (a, b), 2 wt % of PVP 360 (c, d), and 5 wt % of PVP 360 (e, f) at pH 2.5 and pH 11. The dosages of other ingredients are 0.5 mol/L DM, ethanol/water ratio of 1:9 (v/v), and 0.5 wt % MBA. All the samples are carried out on purified dilute dispersions. Scale barD5m (Reproduced with permission from Ref. [24], Copyright (2007), Elsevier)
have relatively low degree of pH responsivity (Vmax/VminD6.6) because of their low content of amine groups resulting in relatively weak electrostatic repulsive forces.
Consequently, the microgels prepared with 2 wt % PVP 360 with moderate size has the highest degree of pH responsivity (Vmax/VminD11.7).
7.4 Monodisperse Cationic pH-Responsive
Fig. 7.10 (a) Hydrodynamic diameters of PDM microgels prepared with 10 wt % of PVP K30 (ı), 2 wt % of PVP 360 (˙), and 5 wt % of PVP 360 () at different pH values and (b) the maximum pH-dependent volume-change ratios of PDM microgels prepared with different PVP. The dosages of other ingredients are 0.5 mol/L DM, ethanol/water ratio of 1:9 (v/v), and 0.5 wt % MBA. All the samples are carried out on purified dilute dispersions (Reproduced with permission from Ref.
[24], Copyright (2007), Elsevier)
Table 7.1 The compositions of different monomer aqueous fluids (Reproduced with permission from Ref. [26], Copyright (2011), Elsevier)
Code DM (M) AAm (M) MBA (M) pH
1# 1.0 / 0.050 4.3
2# 1.0 / 0.050 7.8
3# 1.0 / 0.025 4.3
4# 1.0 / 0.100 4.3
5# 1.5 / 0.075 7.8
6# 1.0 0.1 0.050 4.3
Note: In the monomer fluids, deionized water is used as solvent and concentrated HCl is used to modulate pH of the solution
Monodisperse PDM hollow microcapsules with cationic pH-responsive property are successfully prepared using oil-in-water-in-oil (O/W/O) double emulsions as the polymerization templates [26]. The compositions of monomer aqueous fluids are listed in Table 7.1. As illustrated in Fig. 7.11a, the emulsion templates are generated in a capillary microfluidic device according to the previous work [17].
Soybean oil containing 3 % (w/v) PGPR and 0.1 % (w/v) Sudan III is used as the inner fluid, and soybean oil containing 5 % (w/v) PGPR is employed as the outer fluid. The middle fluid is monomer aqueous solution containing monomer DM, cross-linker MBA, surfactant Pluronic F127 (1 %, w/v), initiator 2,2’-azobis(2- amidinopropane dihydrochloride) (V50) (0.05 %, w/v), and glycerin (5 %, w/v). The generated O/W/O emulsions are collected in a beaker containing excess soybean oil which contains 5 % (w/v) PGPR and 1 % (w/v) photo-initiator 2,2-dimethoxy-2- phenylacetophenone (BDK). The cross-linked PDM microcapsules are prepared via
7.4 Monodisperse Cationic pH-Responsive Hydrogel Capsules 165
Fig. 7.11 Schematic illustration of the capillary microfluidic device for generating O/W/O emulsions (a), and optical microscope images of sample 2# O/W/O emulsions (b) and PDM microcapsules in buffer solution of pH 7.4 at 37ıC (c). The scale bars are 100m (Reproduced with permission from Ref. [26], Copyright (2011), Elsevier)
UV-initiated polymerization in an ice bath for 30 min. A double initiation system composed of water-soluble V50 and oil-soluble BDK photo-initiators is applied to ensure the successful synthesis of PDM microcapsules. Under UV irradiation, the oil-soluble photo-initiator dissociates to generate a great deal of active free radicals that diffuse across the oil-water interface to the water phase of O/W/O emulsions to start the polymerization at the oil-water interface. Such interface initiation would ensure the obtained microcapsules being of a good sphericity. On the other hand, the water-soluble photo-initiator in water phase can initiate the monomers to polymerize sufficiently.
The optical microscope image of O/W/O emulsions prepared by the microfluidic technique is shown in Fig.7.11b, and the optical image of PDM microcapsules polymerized from these double emulsions is shown in Fig. 7.11c [26]. It can be clearly seen that the obtained O/W/O emulsions and PDM microcapsules exhibit good spherical shape and monodispersity and the PDM microcapsules present obvious hollow cavity structures.
The membrane of the prepared microcapsule is composed of cross-linked PDM, which can swell in acidic environment due to the protonation ofN(CH3)2groups in the polymeric network. The effects of various preparation parameters, such as pH value of the monomer solution, concentrations of MBA cross-linker, concentration of DM monomer, and addition of copolymeric monomer acrylamide (AAm), on the
Fig. 7.12 Diameters (a) and pH-responsive swelling ratios (b) of PDM microcapsules prepared at different pH. The test temperature is 37ıC (Reproduced with permission from Ref. [26], Copyright (2011), Elsevier)
pH-responsive characteristics of the PDM microcapsules are systematically studied [26]. The swelling ratios of membrane thickness (ıpH/ı7.4) induced by external pH changing from 7.4 to certain pH are defined to characterize the pH-responsive behaviors of prepared PDM microcapsules.
Figure7.12shows the diameters and pH-responsive swelling ratios (ıpH/ı7.4) of PDM microcapsules prepared at different pH (1# and 2#) [26]. The microcapsule prepared at pH 4.3 is smaller than the microcapsule prepared at pH 7.8 when they are immersed in the same buffer solution (Fig.7.12a). Both PDM microcapsules exhibit obvious pH-responsive characteristics that the membrane thickness increases with decreasing external pH value, as shown in Fig. 7.12b. Interestingly, the swelling ratios of PDM microcapsule prepared at pH 4.3 are lower than that prepared at pH 7.8. Figure7.13illustrates the explanation of these pH-responsive phenomena. When the pH value of monomer aqueous fluid is 4.3, the network of PDM microcapsules has already swollen to some extent due to the partial protonation of N(CH3)2 groups during the preparation process. Therefore, the length of the polymeric chain between two cross-linking points is shorter due to the electrostatic repulsion of protonatedN(CH3)2 groups, which leads to lower pH- responsive swelling ratios, as shown in Fig.7.13a. Moreover, in the network of PDM microcapsules prepared at pH 4.3, the number ofN(CH3)2groups with protonation ability decreases, which would also lead to a lower swelling ratio when these microcapsules are put in acidic solution. On the contrary, the PDM microcapsules prepared at 7.8 have a longer polymeric chain between two cross-linking points because the PDM network is in a shrunken state during the preparation process.
Therefore, the PDM microcapsules prepared at pH 7.8 exhibit larger swelling ratio than those prepared at pH 4.3, as shown in Fig.7.13b.
Figure 7.14 shows the diameters and pH-responsive swelling ratios of PDM microcapsules prepared with different concentrations of cross-linker MBA [26]. It can be observed that, with the increase of cross-linking degree, both the outer and
7.4 Monodisperse Cationic pH-Responsive Hydrogel Capsules 167
Fig. 7.13 Schematic illustration of pH-responsive mechanism of cross-linked PDM polymeric network prepared at different pH: (a) pHD4.3 and (b) pHD7.8 (Reproduced with permission from Ref. [26], Copyright (2011), Elsevier)
Fig. 7.14 Diameters (a) and pH-responsive swelling ratios (b) of PDM microcapsules prepared with different MBA concentrations. The test temperature is 37ıC (Reproduced with permission from Ref. [26], Copyright (2011), Elsevier)
inner diameters of PDM microcapsules decrease in the same buffer solution. As shown in Fig.7.14b, all prepared PDM microcapsules exhibit good pH-sensitivities that the swelling ratios of membrane thickness increase with the decrease of pH in the external solution. Specially, the swelling ratios of PDM microcapsules also decrease with increasing the cross-linking degree of polymeric network. The increase of cross-linking degree would result in a decreased elasticity of the network and then a decreased swelling ratio.
The effect of monomer DM concentration on the pH-responsive swelling ratios of microcapsules is also investigated by keeping the same molar ratio of [MBA]/[DM]
Fig. 7.15 Diameters (a) and pH-responsive swelling ratios (b) of PDM microcapsules prepared with different DM concentrations. The test temperature is 37ıC (Reproduced with permission from Ref. [26], Copyright (2011), Elsevier)
Fig. 7.16 Diameters (a) and pH-responsive swelling ratios (b) of PDM microcapsules prepared with the addition of AAm. The test temperature is 37ıC (Reproduced with permission from Ref. [26], Copyright (2011), Elsevier)
as 0.050/1. The size of PDM microcapsules in buffer solution of pH 7.4 decreases with increasing the DM content, as shown in Fig.7.15a [26]. PDM microcapsules with lower DM content also show larger pH-responsive swelling ratios than those with higher DM content. To keep the same molar ratio of [MBA]/[DM], the cross- linker concentration also increases with increasing the DM concentration, which results in a larger density of the polymeric network and a decreased aperture of the PDM network.
The PDM microcapsules are also prepared by adding another comonomer AAm with no pH sensitivity. The PDM-based copolymeric microcapsules also have pH sensitivity, but the swelling ratios decrease, as shown in Fig.7.16[26]. The reason is that the formation of hydrogen bonds between amide groups in AAm andN(CH3)2
References 169
groups in DM would protect N(CH3)2 groups from exposing to the outside [27]. Therefore, the protonation ability ofN(CH3)2 groups decreases, and then a decrease of pH-responsive swelling ratio results.
The above results show that, when PDM microcapsules are prepared at high pH and with low cross-linking density and low DM monomer concentration, they exhibit high pH-responsive swelling ratios. The addition of copolymeric monomer AAm decreases the swelling ratios of PDM microcapsules. The prepared PDM microcapsules with both biocompatibility and cationic pH-responsive properties are of great potential as drug delivery carriers for tumor therapy. Moreover, the fabrication method and research results provide valuable guidance for preparation of core-shell microcapsules via free-radical polymerization based on synergistic effects of interfacial initiation and initiation in confined space.