Design and Characterization of GelMA Nanogels (nanoGelMA) via Desolvation and Photopolymerization for Drug Delivery Applications

Background/Objectives: Micro- and nano-scale hydrogels (microgels and nanogels) have attracted increasing attention as carriers for drug delivery due to their high-water content, responsiveness to external stimuli, tunable properties, and versatility. In this work, gelatin methacryloyl (GelMA) with a medium degree of methacryloylation (DoM ca. 60%) was ad hoc synthesized as a constituent material for nanogel production. For the first time in the literature, GelMA-based nanogels (nanoGelMA) were developed through an optimized two-step desolvation method combined with photo-crosslinking. Methods: The influence of key process parameters, including the pH, volume of desolvating agent, photo-initiator concentration, and UV exposure time, was systematically investigated to identify optimal conditions for nanoGelMA preparation. To assess its potential as a drug delivery nanocarrier, the nanoGelMA was loaded with ibuprofen (IBU) as a model anti-inflammatory drug via in situ encapsulation during nanogel preparation. Results: The formulated nanoGelMA exhibited an average hydrodynamic diameter (d) of ca. 250 nm, a polydispersity index of 0.2, and a production yield of approximately 30%. The nanogels demonstrated stability in water and in phosphate buffer at pH 5 over 96 h, while exhibiting significant swelling in physiological-like conditions and enzymatic degradation (d of ca. 421 ± 91 nm and 609 ± 182 nm at 96 h, respectively). The cytocompatibility evaluation demonstrated high cell viability (86–96%) of the nanoGelMA at different concentrations (1–5 mg/mL). IBU-loaded nanoGelMA particles were successfully developed via direct drug encapsulation during nanogel formation, achieving a maximum encapsulation efficiency of ca. 30%, and exhibited environment-responsive release, with kinetics modulated by the ionic strength, pH, and enzymatic activity. Conclusions: Overall, the nanoGelMA developed herein represents a promising nanogel platform with great potential for the development of advanced and controlled drug delivery therapies.