Preparation and Sustained Drug Release Study of Interpenetrating Network PNIPAm/SA(Ca2+) Hydrogels

Abstract

A polyaspartic acid derivative was synthesized as a crosslinking agent (AEA-PSI), and its structure was analyzed using proton nuclear magnetic resonance (¹H NMR) and Fourier transform infrared spectroscopy (FTIR). A temperature- and pH-responsive hydrogel based on sodium alginate (SA) and N-isopropylacrylamide (NIPAm) was synthesized and characterized by FTIR, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and mercury intrusion porosimetry (MIP) to confirm its structure and thermal stability. The formulation was systematically optimized by varying SA content, NIPAm concentration, and crosslinker dosage, yielding hydrogels with tunable swelling capacity and network structure. Incorporating AEA-PSI refined the three-dimensional network without compromising its temperature- and pH-responsive behavior. This tailored structure facilitated sustained drug release: the optimized hydrogel exhibited significantly higher 5-fluorouracil (5-FU) release in simulated intestinal fluid (SIF, pH = 7.4, 90.19%) compared to simulated gastric fluid (SGF, pH = 1.2), with release kinetics following the Ritger–Peppas model. Furthermore, the hydrogel demonstrated superior biodegradability in intestinal fluid and lysozyme solution, a functional advantage rarely achieved in conventional alginate-based hydrogels. This work presents a successful valorization of natural and synthetic polymers into a tunable and biocompatible drug-delivery platform, achieving a synergistic combination of responsiveness, sustained release, and biodegradability for the treatment of small intestine–related diseases.