Dual‐Stimuli Responsive Poly( N ‐acryloyl glycine) Microgels: Investigation of Network Structures and Application for Loading and Release of Biologics

ABSTRACT

Poly( N ‐acryloyl glycine) (PNAG) bulk hydrogels are known to exhibit pH‐ and ion‐responsive behavior. In this study, PNAG hydrogel particles were prepared by droplet‐based microfluidics in combination with in situ photopolymerization. Rheological investigations led to the optimization of the PNAG gelation kinetics by the choice of photoinitiators, buffer media (pH 3, 7.4, or 9), and calcium ion (Ca ²⁺ ) concentrations (none or 5 wt.% CaCl ₂ ). The microparticles demonstrated a strong swelling response, with a volume increase of over 5000 vol.% upon pH shifts. Rheology and multiple‐quantum nuclear magnetic resonance (MQ‐NMR) further revealed pronounced differences in network constraints and chain mobility between the investigated conditions. Via pH‐induced swelling, model biopharmaceuticals such as glutathione (GSH) were loaded into the particles by soaking, followed by compound entrapment through Ca ²⁺ ‐induced network constriction, leading to high drug payloads >20 wt.%. Drug release studies revealed an initial burst release, followed by a remarkable prolonged diffusion‐controlled release for about 2 weeks. As PNAG hydrogel particles demonstrated their potential for drug delivery, further studies could explore the tailoring of mesh sizes and broaden the spectrum of investigated biopharmaceuticals.