# Smart Poly(acrylic acid)/Poly(acrylamide) Microgels with Interpenetrating Polymer Network Structure
## 4 Discussion  
Microgels based on poly(acrylic acid) are pH responsive and suitable for oral drug delivery. At the low pH of the stomach, such microgels retain their hydrophobic, collapsed state, providing both protection of the drug against degradation in the stomach and minimal stomach release. This has been shown to be beneficial for the oral delivery of different drugs [28,29]. In addition, the targeted intestinal delivery may be beneficial for the treatment of certain diseases. A study from [PERSON] et al. demonstrates the delivery of siRNA to the intestinal regions with poly(methacrylic acid-co-N-vinyl-2-pyrrolidone) nanogels, owing the potential for the treatment of inflammatory bowel disease [30]. In this study, a series of PAA/PAAM MGs with an IPN structure and varying weight fractions of the PAA component were obtained. All IPN MG as well as the PAA SN MGs exhibited pH-dependent swelling behavior, as revealed by DLS (Figure 2). At pH-5, the pendant -COOH groups of PAA started to deprotonate and turn into -COO\({}^{-}\) anions, like their bulk analogues we synthesized previously [21]. Under physiological conditions where the gastric pH is \(\sim\)1.2, i.e., below the pKa, and pH-7.4 in the intestines [31], such behavior is beneficial for the delivery of drug molecules to the intestine. As has been demonstrated, this can provide a sustained drug release profile with enhanced drug bioavailability [32]. [PERSON] et al. demonstrated that hydrogel particles of bacterial cellulose grafted with poly(acrylic acid) show a pH-responsive in vitro release of insulin to the colon, thus improving its oral bioavailability and exhibiting better hypoglycemic effects [33]. The \(\mid\)ZP  
Figure 10: AF4 tractograms for samples PC 50 (**A**), molar masses (symbols) and PC 75 (**B**), and PC 33 (**C**), \(\rm{R_{h}}\) (symbols); LS signal (solid line), RI signal (broken line) vs. elution time. is known to directly affect the stability of suspensions as well as the interaction between charged drugs and polymeric microspheres [34]. The \(\mid\)ZP\(\mid\) values of the SNs and IPNs synthesized in this study showed a tendency to decrease with increasing pH up to pH-5, while their values decreased from \(-\)\(-\)5 mV to \(-\)\(-\)40 mV, depending on the MG composition (Figure 4). [PERSON] et al. studied the potential of polyanionic pH-sensitive poly(2-acrylamide-2-methyl-1-propanesulfonic acid) (PAMPS) for the controlled delivery of the cationic drug doxorubicin. It was shown that the electrostatic attraction forces between the sulfonate groups of PAMPS favor drug loading and allow for a controlled release patterns with cumulative Dox release of 20% and 70% at pH 7.4 and 5.5, respectively [35]. Similarly, PAA/PAAM IPN MGs can be beneficial for the controlled release of cationic drugs by electrostatic attraction determined by the PAA pendant -COO\({}^{-}\) groups at pH levels above pKa. Another factor contributing to the in vivo performance of such microgels is their temperature responsiveness. As was revealed by NMR, the temperature responsiveness of the PAA/PAA MGs was determined by pH (Figures 7 and 9). Such pH-defined temperature responsiveness is reported for the \"straight\" PAAM/PAA IPN nanopgels at pH = 3 [12]. The authors report an abrupt change in the swelling degree of the IPN MGs as compared to the PAA-co-PAAM MGs at pH = 3. The higher pH at which we observed temperature responsiveness could be explained in terms of the parameters that influence the formation of PAA-PAAM interpolymer complexes. [PERSON] et al. [36] have reported that three parameters influence the critical pH values of the complexation between PAA and PAAM, namely an increase in polymer concentration, the molecular weight of PAA, and ionic strength favor the complexation and shift the critical pH values to the higher pH region. Thus, the high polymer content in the IPNs most probably contributed to the higher pH at which the formation of the PAA-PAAM complex started.