PNIPAAm

Many kinds of nonbiodegradable vinyl-type hydrophilic polymers were also used in combination with aliphatic polyesters to prepare amphiphilic block copolymers. Two typical examples of the vinyl-polymers used are poly(/V-isopropylacrylamide) (PNIPAAm) [149-152] and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) [153]. PNIPAAm is well known as a temperature-responsive polymer and has been used in biomedicine to provide smart materials. Temperature-responsive nanoparticles or polymer micelles could be prepared using PNIPAAm-6-PLA block copolymers [149-152]. PMPC is also a well-known biocompatible polymer that suppresses protein adsorption and platelet adhesion, and has been used as the hydrophilic outer shell of polymer micelles consisting of a block copolymer of PMPC -co-PLA [153]. Many other vinyl-type polymers used for PLA-based amphiphilic block copolymers were also introduced in a recent review [16]. 

PNIPAAm-based hydrogel Hydrophobic interaction Temperature [30]... 

Chen and Hoffman prepared new graft copolymers of PAA and PNIPAAm that responded more rapidly to external stimulus than previously studied materials (Chen and Hoffman, 1995). These materials... 

Methoxy poly(ethyleneglycol) (mPEG) was the most frequently used semitelechelic polymer for over 2 decades. It has been successfully used for the modification of various proteins, biomedical surfaces and hydrophobic anticancer drugs (for reviews see References [3,9,10]. Recently, a number of new semitelechelic (ST) polymers, such as ST-poly(A -isopropylacry-lamide) (ST-PNIPAAM) [11-15], ST-poly(4-acryloylmorpholine) (ST-PAcM) [16], ST-poly(A-vinylpyrrolidone) (ST-PVP) [17], and ST-poly[A-(2-hydroxypropyl)methacrylamide] (ST-PHPMA) [18-21] have been prepared and shown to be effective in the modification of proteins or biomedical surfaces. 

Poly(A-isopropyl acrylamide) (PNIPAAm) is the most extensively studied temperature-sensitive polymer [10-20]. Crosslinked PNIPAAm exhibits drastic swelling transition at its lower critical solution temperature... 

In this work, we generated new PMAA/PNIPAAm IPN hydrogels with both pH and temperature sensitivities by the interpenetration of the pH-sensitive and temperature-sensitive polymer networks. 

The temperature-sensitive poly(A-isopropyl acrylamide) and pH-sensitive poly(methacrylic acid) were used as the two component networks in the IPN system. Since both A-isopropyl acrylamide (NIPAAm) (Fisher Scientific, Pittsburgh, PA) and methacrylic acid (MAA) (Aldrich, Milwaukee, Wl) react by the same polymerization mechanism, a sequential method was used to avoid the formation of a PNIPAAm/PMAA copolymer. A UV-initiated solution-polymerization technique offered a quick and convenient way to achieve the interpenetration of the networks. Polymer network I was prepared and purified before polymer network II was synthesized in the presence of network I. Figure I shows the typical IPN structure. 

Figure 2 Equilibrium swelling behavior as a function pH at 22°C in pH buffer solution for PMAA/PNIPAAm IPN samples ( ) containing 70 mol% of PNIPAAm and pure PMAA ( ) samples.

Figure 4 Equilibrium swelling behavior as a funetion of ionie strength at pH 7.0, 22°C for PMAA/PNIPAAm IPN (O), PMAA ( ), and PNIPAAm (A).

DSC were conducted on PMAA/PNIPAAm IPN hydrogels swollen at different pH values. The results show that the difference in pH has great influence on the LCST transitions of the IPN hydrogels, as shown in Figure 5. 

At pH 4.3, there is no significant transition detected around 32°C. Transition temperatures are detected and increase as pH increases. This is because, at low pH, the aggregation of PMAA decreases the mobility of the PNIPAAm network as well as the water uptake of the IPN, resulting in drastically lowering the temperature sensitivity of the IPN hydrogel. However, at higher pH value, the swollen PMAA allows the PNIPAAm to have a higher mobility, which makes the IPN more temperature sensitive. 

Compared to the DSC diagram of pure PNIPAAm, we noticed that the LCST transitions detected in the IPNs samples were in the range of 31-32°C. There was no significant deviation from the LCST of the pure PNIPAAm, which was the major difference between a PNIPAAm-based IPN and a PNIPAAm copolymer in which the LCST will be greatly influenced by the comonomers. Thus, the formation of IPN gave a relatively independent polymer system in which each network may retain its own property. 

Figure 5 Differential seanning ealorimetry thermograms of PMAA/PNIPAAm IPNs at pH 4.4, 5.3, 7.4, and 8.0.

Shown in Figure 6 is a plot for the permeation of the four different model drugs through a PMAA/PNIPAAm IPN membrane containing 70 mol% of PNIPAAm in pH 7.4 buffer solution. As mentioned, the slope of each linear curve represents the permeability of each solute. As expected, higher permeability was observed for smaller model drug. From theophylline to FITC-Dextran, the permeability decreases, which is an indication of the size exclusion behavior in the IPN membrane at the same gel swollen state, the IPNs show higher permeability for the smaller solutes. 

Figure 6 Solute permeation of theophylline (O), proxyphylline ( ), oxprenolol HCl (A), and FITC-Dextran (V) through PMAA/PNIPAAm IPN. The slope represents the permeability of each solute.

Interpenetrating polymer networks of PMAA/PNIPAAm were prepared. The material exhibited both pH and temperature sensitivities. The temperature sensitivity was verified by DSC studies. The permeation studies showed a significant size exclusion phenomenon of the IPNs. The influence of pH and temperature on the IPN permeability was investigated. A hypothetical mechanism was presented to explain the high permeability at high temperature and high pH. 

---