An ATR-FTIR-Based Screening Strategy for Formulation–membrane Interactions and Invertebrate Oxidative Stress Signatures

The growing demand for alternative and innovation-driven screening methodologies in pharmaceutical and cosmetic research has stimulated the development of complementary physicochemical and biological evaluation platforms. This study explored an ATR-FTIR–based screening strategy using Strat-M® synthetic membranes and an invertebrate oxidative stress model based on Tenebrio molitor larvae. Semisolid formulations containing spray-dried NC-HT-TiO₂ or NC-TiO₂ were incorporated into a gel-cream base and applied to Strat-M® membranes, followed by ATR-FTIR spectral analysis to assess formulation–membrane interactions and infrared attenuation profiles. Formulations G3 and G6 demonstrated the greatest reduction in transmittance (approximately 30–40% and 25–30%, respectively), compared to 60–65% for the vehicle. In parallel, T. molitor larvae were exposed to bioactive compounds (farnesol, hesperetin, and silibinin) prior to H₂O₂-induced oxidative stress, and hemolymph samples were analyzed by ATR-FTIR to evaluate changes in the O–H stretching region (3200–3600 cm⁻¹). Concentration-dependent spectral variations were observed, particularly for hesperetin and silibinin, consistent with oxidative stress–associated molecular alterations. To our knowledge, this is the first study to combine Strat-M®-based ATR-FTIR formulation analysis with an ATR-FTIR readout of oxidative stress signatures in T. molitor, proposing a proof-of-concept dual-model screening approach. These findings support the potential of ATR-FTIR as a complementary tool for early-stage evaluation of formulation interactions and bioactive compound performance.