Biofunctional Polymer-Based Platforms for Controlled Delivery of STING Inhibitors

The STING (stimulator of interferon genes) signaling pathway plays an important role in the regulation of innate immune responses and has emerged as a promising therapeutic target in conditions associated with excessive or dysregulated inflammation. The development of suitable delivery systems may improve the local availability of STING inhibitors and enable their controlled release. Therefore, the aim of this study is to develop and optimize polymer-based matrices as potential platforms for the delivery of STING-targeting compounds.

Several natural and synthetic polymer systems were screened with particular emphasis on their physicochemical stability and ability to maintain structural integrity during incubation. Among the investigated materials, albumin and poly(vinylpyrrolidone) (PVP) showed the highest potential. Albumin-based matrices containing 30% polymer were prepared using thermal crosslinking, while UV-induced crosslinking was also evaluated. PVP-based matrices containing 15% polymer were crosslinked by UV irradiation using polyethylene glycol diacrylate (PEGDA, Mn ≈ 700 g/mol) as a crosslinking agent and 2-hydroxy-2-methylpropiophenone as a photoinitiator. The developed materials were characterized in terms of their structural and surface properties, swelling behavior, degradation, and stability under incubation conditions.

Preliminary screening demonstrated clear differences in the stability of the investigated polymer systems. Several initially tested formulations rapidly lost their structural integrity or disintegrated during the early stages of incubation, whereas the selected albumin- and PVP-based systems maintained their geometry and remained stable during prolonged incubation. Moreover, incubation in simulated body fluids showed stable pH conditions over a 14-day period, indicating that the selected matrices did not induce substantial changes in the surrounding medium. Biofunctionalization in the present study refers to the incorporation of H-151, a STING inhibitor, directly into the polymer matrices during synthesis. H-151 was incorporated at a loading corresponding to a theoretical maximum concentration of 5 µM in the release medium, assuming complete release of the incorporated compound. H-151-containing formulations were successfully prepared, and studies evaluating its release from the selected matrices are currently in progress.

These preliminary results identify albumin- and PVP-based matrices as promising candidates for the further development of tunable polymer platforms for the delivery of STING inhibitors.