Nanoparticle-Embedded GelMA/NIPAm Hydrogels: A Temperature-Responsive Hybrid System for Controlled Drug Release.

Abstract

Temperature-responsive hydrogels incorporating drug-loaded polymeric nanoparticles represent a significant advancement in controlled release systems, enabling responsive and environmentally triggered drug delivery. In this study, a novel temperature-responsive drug delivery system was developed based on a gelatin methacryloyl/N-isopropylacrylamide (GelMA/NIPAm) hydrogel incorporating phenytoin (PHT)-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. For this, empty nanoparticles, PHT-loaded nanoparticles, bare hydrogels (BH), empty nanoparticle-loaded hydrogels (eNP-H), and PHT-encapsulated nanoparticle-embedded hydrogels (PHT-H) were prepared and characterized using FTIR, SEM, DSC, XRD, DLS, swelling, drug release, and biocompatibility tests. The drug-loaded nanoparticles exhibited hydrodynamic diameter of 223.7  ±  8.4 nm with a PDI of 0.298 and a zeta potential of -20.4 mV. The BH, eNP-H, and PHT-H hydrogels displayed similar temperature-dependent swelling, with approximate weight swelling ratios of 9.0 at 25°C, 7.5 at 37°C, and 6.0 at 40°C. Swelling kinetics showed that all hydrogels reached equilibrium within 20 min. Moreover, the hydrogels demonstrated consistent cyclic swelling and shrinking at 37°C and 40°C. Drug release studies revealed that PHT-H hydrogels released ∼20% of phenytoin at 37°C and ∼34% at 40°C over 7 days, confirming sustained, temperature-responsive drug release. Cell viability assays indicated no cytotoxicity and potential promotion of cell proliferation. Thus, these hydrogels offer a promising platform for efficient, temperature-sensitive, and controlled drug delivery applications.