(291c) Microrheological Characterization of Covalent Adaptable Hydrogel Degradation in Response to pH Changes That Mimic the pH in the Gastrointestinal Tract

Covalent adaptable hydrogels (CAHs) are composed of network bonds that can reversibly break and reform in response to external stimuli, including addition of external force or change in environmental conditions. This stimuli-responsive nature is due to the incorporation of dynamic covalent chemistry into the polymeric scaffold. This chemistry results in stimuli-responsive structural evolution, which makes CAHs ideal for biological applications ranging from bio-ink for 3D-printing to pH responsive drug delivery vehicles. To design a CAH as a drug delivery vehicle, specifically for oral drug delivery, scaffold degradation in response to pH changes that mimic the native pHs in the gastrointestinal (GI) tract must be characterized. Our work focuses on characterization of the degradation of a self-assembled CAH consisting of 8-arm star poly(ethylene glycol) (PEG)-hydrazine and 8-arm star PEG-aldehyde, which create dynamic covalent hydrazone bonds. To mimic changes in pH through the digestive tract and simultaneously characterize scaffold degradation, we use μ²rheology. μ²rheology enables multiple particle tracking microrheological characterization in a microfluidic device. In multiple particle tracking microrheology (MPT), fluorescent probe particles are embedded in a sample and their Brownian motion is measured to extract material rheological properties. To mimic changes in the pH environment in each part of digestive tract, we use a two-layer microfluidic device. Our device allows the fluid environment to be exchanged around a single sample with minimal sample loss, regardless of the state of the sample. Using μ²rheology, we characterize CAH degradation at a single pH (pH 4.3, 5.5 and 7.4), with a single pH exchange (pH 4.3 to 7.4 and pH 7.4 to 4.3) and during temporal pH changes that mimic the pH in the entire GI tract. To characterize the critical phase transition between a gel and a sol, the critical relaxation exponent is calculated from single pH and single pH exchange experiments. This value quantitatively identifies the state of the material, pinpoints where the phase transition occurs and identifies the material microstructure at the phase transition. The critical relaxation exponent for this scaffold is independent of incubation pH, indicating that the material microstructure and phase transition are also independent of incubation pH. From measurements of single pH exchange and temporal pH changes through the whole GI tract, we determine that degradation history has no impact on CAH degradation kinetics and material property evolution. However, the initial cross-link density of the scaffold at each pH exchange can be reduced by previous degradations, which reduces the time to reach the gel-sol transition. For applications of molecular delivery, this change in degradation time will impact release. These results indicate degradation can be tuned by changing scaffold cross-link density, which can be done by changing polymer concentration or the ratio of functional groups. This work will inform design of this CAH for site-specific oral drug or nutrient delivery.