Tunable Drug Release through Varying Drug Affinities for Ocular Chronic Disease.

Effective drug delivery is critical for the management of chronic diseases such as glaucoma, where sustained therapeutic levels can significantly enhance treatment outcomes. In this study, we present a Particles-on-a-Gel (PoG) system that leverages differential nanocarrier affinities to modulate drug release kinetics. By integrating poly(N-isopropylacrylamide) nanogels (pNIPAM) and silver nanoparticles (AgNPs), the PoG platform enables both controlled initial release and prolonged drug delivery. Isothermal titration calorimetry (ITC) was employed to quantitatively characterize the thermodynamic interactions between timolol maleate and the nanocarriers, revealing distinct binding modalities─hydrophobic interactions with pNIPAM and chemically driven binding with AgNPs. These findings underscore the role of thermodynamic tuning in optimizing drug-carrier interactions to enhance release profiles and retention. Furthermore, incorporation of the PoG system into a contact lens-based drug delivery platform demonstrated its translational potential, maintaining optical transparency while enabling sustained drug release. Overall, this work highlights the promise of thermodynamically guided nanocarrier design in developing patient-centric drug delivery systems for chronic disease management.