in the Porous Membranes as Gates
As mentioned above, to make the thermo-responsive microcapsules more suitable for DDS, it is essential to develop monodispersed small-sized thermo-responsive microcapsules. Recently, the monodispersed thermo-responsive microcapsules with a mean diameter of about 4m have been successfully prepared, which are com- posed of porous polyamide membranes and PNIPAM-grafted gates [4]. By virtue of SPG membrane emulsification technique, the small-sized monodispersed oil-in- water (O/W) emulsions are generated and then form core-shell porous polyamide microcapsules via interfacial polymerization. The PNIPAM chains are grafted into the pores of the microcapsule membranes by plasma-induced pore-filling graft polymerization.
Figure6.1shows the thermo-responsive release of NaCl from PNIPAM-grafted microcapsules with a mean diameter of about 4m. The NaCl concentration of the bulk solution increases slowly at 25ıC and rapidly at 40ıC; that means the release of NaCl from the PNIPAM-grafted microcapsules is slow at 25ıC and fast
Fig. 6.1 Thermo-responsive release of NaCl from the PNIPAM-grafted
microcapsules with a mean diameter of about 4m (Reproduced with permission from Ref. [4], Copyright (2002), American Chemical Society)
at 40ıC. At temperatures below the lower critical solution temperature (LCST), the PNIPAM-grafted chains in the pores of the microcapsules are swollen and the membrane pores are closed by the PNIPAM gates. As a result, the release of NaCl molecules across the microcapsule membranes is slow. In contrast, at temperatures above the LCST, the PNIPAM-grafted chains in the membrane pores are shrunk, and therefore, the pores of the microcapsule membranes are open and resulted in a faster release rate of the NaCl molecules across the microcapsules. Therefore, the release rate of the solute molecules from this kind of PNIPAM-grafted microcapsules at higher temperatures (above the LCST) is greater than that at lower temperatures (below the LCST). The prepared PNIPAM-grafted microcapsules with a mean diameter of about 4 m show satisfactory reversible and reproducible thermo- responsive release characteristics. Similar to that of NaCl, the release of vitamin B12 (VB12) from the PNIPAM-grafted microcapsules is slow at 25ıC and fast at 40ıC, which is also due to the closed-open state of the grafted “gates”. The diffusion thermo-responsive coefficient RDDP40/P25 of the PNIPAM-grafted microcapsules toward VB12 is much larger than that of NaCl.
Similar to the results of flat membranes in Chap. 5 [9, 20–22], the pro- posed thermo-responsive microcapsules could exhibit a positive thermo-responsive controlled-release mode or a negative thermo-responsive one by changing the PNI- PAM grafting yield [5]. The thermo-responsive controlled-release characteristics of VB12 from PNIPAM-grafted microcapsules with different grafting yields are illus- trated in Fig.6.2. At low grafting yields, the PNIPAM-grafted microcapsules show a positive thermo-responsive controlled-release mode, while at high grafting yields,
138 6 Functional Microcapsules with Thermo-responsive Hydrogel Shells
Fig. 6.2 Thermo-responsive controlled release of VB12 from PNIPAM-grafted microcapsules with different grafting yields (Reproduced with permission from Ref.
[5], Copyright (2001), Elsevier)
they show a negative thermo-responsive controlled-release mode. At temperature above the LCST, the pores of PNIPAM-grafted microcapsules with low grafting yield are open, and solute diffusion occurs within the pores with the openings larger than the solute size. However, the pores are closed due to swollen PNIPAM gate at temperature below the LCST, and solute diffusion occurs within the PNIPAM hydrogels. Therefore, the permeability coefficient of VB12 from the microcapsules is higher at temperatures above the LCST than that below the LCST, due to the
“open-closed” pores in the microcapsule membranes controlled by the PNIPAM gates. The prepared PNIPAM-grafted microcapsules show a satisfactorily reversible and reproducible thermo-responsive controlled release.
In contrast, when the grafting yield of PNIPAM-grafted microcapsules is high, the permeability coefficient of VB12 at temperatures above the LCST is lower than that below the LCST, due to the hydrophilic/hydrophobic phase transition of the PNIPAM gates. At a high grafting yield, because there is too much grafted polymer in the pores of microcapsules, the pores cannot reopen even at high temperatures (above the LCST), i.e., the pore is choked. However, the grafted PNIPAM chains are still highly hydrophilic and water soluble at temperature below the LCST and dramatically become hydrophobic and insoluble in water at temperature above the LCST, with a phase transition. As the solute is water soluble, any solute diffusion within the membrane occurs primarily within the water-filled regions in the spaces delineated by the polymer chains. It is easier for the solute to find water- filled regions in the membrane with hydrophilic PNIPAM gates rather than in the membrane with hydrophobic PNIPAM gates. Therefore, the permeability coefficient of the solute molecules from PNIPAM-grafted microcapsules at low temperatures (below the LCST) is higher than that at high temperatures (above the LCST).
Fig. 6.3 Thermo-responsive permeability coefficients of NaCl from PNIPAM-grafted microcapsules with different grafting yields (Reproduced with permission from Ref.
[5], Copyright (2001), Elsevier)
The thermo-responsive permeability coefficient of NaCl through the PNIPAM- grafted microcapsules with different grafting time is shown in Fig.6.3. In a previous study [23], it was shown that the grafting yield was directly proportional to the grafting time in the plasma-induced pore-filling graft polymerization, with all other experimental conditions being the same. Therefore, the result in Fig.6.3reflects the effect of the grafting yield on the thermo-responsive permeability coefficient of the PNIPAM-grafted microcapsules. It is interesting to note that the grafting yields have an opposite effect on the permeability coefficients of the microcapsules.
It also indicates that two distinct modes of gating functions exist as positive thermo-responsive mode and negative thermo-responsive mode, depending on the grafting yield. It is seen that at shorter grafting times (or lower grafting yield), the permeability at 40ıC is higher than that at 25ıC; while at longer grafting times (or higher grafting yield), the permeability at 40ıC is lower than that at 25ıC.
Based on our previous work [5], a superparamagnetic property is introduced into the porous microcapsule membrane with thermo-responsive gates [24]. Before preparing the microcapsule, oleic acid (OA)-modified Fe3O4 nanoparticles are synthesized using a chemical coprecipitation route followed by coating with OA.
Subsequently, the modified Fe3O4 nanoparticles are introduced to prepare the polyamide microcapsules with magnetic porous membranes during interfacial poly- merization process. Later, the microcapsule membranes are grafted with PNIPAM chains by employing plasma-induced pore-filling graft polymerization. When the temperature is below the LCST, the grafted PNIPAM chains in the magnetic thermo-responsive microcapsule membranes are in the swollen state and the gates of membrane pores are “close”; on the other hand, when the temperature is above the LCST, the PNIPAM chains are in the shrunken state and the gates of membrane pores are “open.” Thus, the release of substance form the microcapsules is controlled by changing the environmental temperature.
140 6 Functional Microcapsules with Thermo-responsive Hydrogel Shells
0 0.5 1 1.5 2
22 25 28 31 34 37 40 43
PVB12 [x108 m/s]
Pore “close”
Temperature [ºC]
Pore “open”
Ungrafted Grafted Fig. 6.4 Thermo-responsive
release of VB12 from ungrafted and PNIPAM- grafted microcapsules with magnetic property
(Reproduced with permission from Ref. [24], Copyright (2008), Elsevier)
The permeability coefficients P of VB12 releasing from ungrafted and PNIPAM- grafted magnetic microcapsules are shown as a function of temperature (Fig.6.4).
For the PNIPAM-grafted microcapsules, the P values are low when the environ- mental temperature is below 31 ıC, and they increase little between 25 ıC and 31ıC. On the other hand, the P values are much higher when the environmental temperature is above 34ıC, while the P values also increase little with temperature increasing from 34ıC to 40ıC. A sharp transition of the permeability coefficient occurs on going from 31ıC to 34ıC, which corresponds to the LCST of PNIPAM (around 32ıC). However, the P value of ungrafted microcapsules does not show such a sharp transition between 31 ıC and 34 ıC under the same experimental conditions. Consequently, the release rate of the solute molecules VB12 from the PNIPAM-grafted microcapsules is much larger at temperatures above the LCST than that below the LCST. The prepared microcapsule membranes exhibit time- independent superparamagnetic property with good magnetic-responsive ability, and satisfactory thermo-responsive controlled-release property. The combined prop- erties of such dual stimuli-responsive microcapsules make them highly attractive for various promising applications, such as site-targeting drug delivery, controlled release of chemicals, microreactors, biomedical and/or chemical sensors, and separations.