# Smart Poly(acrylic acid)/Poly(acrylamide) Microgels with Interpenetrating Polymer Network Structure
###### Abstract  
Microgels with precisely tuned properties are of great importance as drug delivery systems. Here, we report the synthesis of microgel particles (MGs) with an interpenetrating polymer network structure composed of poly(acrylic acid) (PAA) and polyacrylamide (PAAM) for their potential application as cationic drug carriers. The MG properties were investigated via several analytical techniques, such as Dynamic Light Scattering (DLS) and zeta potential (ZP) measurements, Diffusion Nuclear Magnetic Resonance (NMR) spectroscopy, Asymmetrical Flow Field-Flow Fractionation (AF4) and Transmission Electron Microscopy (TEM). The MGs show pH-dependent swelling behavior with a radius of ~100 nm at collapsed state (pH < 4.5) and swell up to ~450 nm (pH-7), while their ZP decreases from ~5 to ~40 mV, depending on their composition. The results of the conducted studies demonstrate the potential of synthesized microgels for drug delivery in the gastrointestinal tract. microgels; poly(acrylic acid); polyacrylamide; interpenetrating polymer networks; drug delivery 29 October 20243 December  
temperature [4] and (ii) polymers with upper critical solution temperature (UCST), where above a certain temperature, the polymer and the respective solvent form a single-phase system [5]. While both types of polymers are within the scope of controlled drug delivery, the UCST systems offer the advantage of complete release of the loaded drug in contrast to LCST systems [6]. Interpenetrating polymer networks (IPNs) are a specific class of polymer materials that could provide well-defined and controllable properties with the proper choice of their constituents as well as of the ratio between them. When polymers with smart responses to different external stimuli are used as IPN constituents, multi-stimuli responsive materials can be obtained. For example, IPNs of poly(acrylic acid) (PAA) and polyacrylamide (PAAM) possess dual stimuli responsiveness to temperature and pH [7; 8]. While the former is due to the hydrogen bonds formed between PAA and PAAM constituent networks, the pH sensitivity is defined by the PAA component: its carboxylic groups have a pKa \(\sim\)4.5-4.9, which makes the polymer neutral below this pH and positively charged above it. This dual-stimuli-responsive behavior is highly valuable for drug delivery. For example, [PERSON] et al. [9] studied the release of losartan potassium from the poly(acrylic acid-co-acrylamide)/gum tragacanth IPN at various pH values and found that the rate of drug release increases with increasing pH. Thus, IPNs are an example of a smart drug delivery system that can release a drug on demand depending on the external environment parameters, e.g., pH or temperature. In a previous study, we found that the pH-responsiveness of bulk PAA/PAAM IPNs depends on their composition--the IPNs with higher PAA content tend to swell more with increasing pH. However, it was not the IPN with the highest PAA content that showed the best drug release (of verapamil hydrochloride, VP), but the IPNs with comparable contents of PAA and PAAM. Thus, the drug release was shown to be dependent on the composition of the IPNs as not only the number of negatively charged carboxylic groups (defined by the PAA content), but also the increase in the IPN network density, due to the higher PAAM content and the associated enhanced hydrogen bond formation, are responsible for such behavior [10]. IPNs of PAA and PAAM are known to exhibit an upper critical solution temperature (UCST) behavior [11; 12; 13], which is evidenced by a strong increase in the IPN swelling ratio with increasing temperature. Moreover, the temperature response of the PAAM/PAA IPN is sigmoidal [13], while the one of the respective copolymers is gradual and less sharp. This is due to the presence of larger blocks of AA and AAM monomer units in the IPN, as compared to their random copolymers [13].