Luteolin Stabilized in Nanosheet and Cubic γ-Cyclodextrin-Based Metal Organic Framework for Enhanced Bioavailability and Anti-inflammatory Therapy

Luteolin (LT), a biologically active flavonoid with potent anti-inflammatory properties, faces significant limitations due to its instability, poor absorption, and low bioavailability. To overcome these challenges, this study explores the encapsulation of LT within nanosheet and cubic γ-cyclodextrin-based metal-organic frameworks (N-MOF and CD-MOF). This approach achieved a two-fold improvement in LT loading efficiency compared to previously reported methods. A critical finding was the identification of pH as a key factor in optimizing the loading process, which significantly enhanced encapsulation efficiency. The resulting LT/N-MOF and LT/CD-MOF formulations demonstrated improved photo-stability and thermal stability, alongside significantly enhanced cellular permeation. In vitro studies revealed remarkable anti-inflammatory properties of these formulations. Moreover, the bioavailability of LT was increased by 6-fold compared to pure luteolin. In a rat paw edema model, the optimized LT/CD-MOF and LT/N-MOF formulations exhibited 4.86- and 5.4-fold improvements in anti-inflammatory activity, respectively, over pure luteolin. These results underscore the potential of CD-MOFs as effective delivery systems for enhancing the therapeutic efficacy of luteolin.