Two-stage photodegradation of indomethacin molecular nanocomposites under extreme confinement

The incorporation of a glassy material into a self-assembled nanoparticle (NP) film can produce highly loaded nanocomposites. Reduction of the NP diameter can lead to extreme nanoconfinement of the glass, significantly affecting the thermal and physical properties of the nanocomposite material. Here, we investigate the photostability and photodegradation mechanisms of molecular nanocomposite films (MNCFs) produced from the infiltration of indomethacin (IMC) molecules into self-assembled films of silica NPs (11-100 nm in diameter). Upon UV irradiation in ambient conditions, IMC degrades in a two-stage process. We demonstrate that nanoconfinement only enhances the photostability of IMC during stage 1, which primarily involves decarboxylation and oxidation. These reactions are kinetically limited by the diffusion of CO₂ and O₂ and are thus affected by the increased glass transition temperature, T_g, and viscosity under confinement. In contrast, during prolonged UV exposure in ambient conditions, stage 2 of IMC degradation, which involves further reactions with water, is unaffected by confinement. This is attributed to the availability of locally adsorbed water in the nanocomposite under ambient conditions, which does not rely on transport through the confined matrix. Overall, unlike previous reports in inert environments, IMC photodegradation in ambient conditions cannot be improved by confinement. These findings highlight the significance of specific degradation pathways in determining whether a material can be stabilized through extreme nanoconfinement.