Supramolecular Structure of the β-Cyclodextrin Metal–Organic Framework Optimizes Iodine Stability and Its Co-delivery with l-Menthol for Antibacterial Applications

The spread of upper respiratory tract (URT) infections harms people’s health and causes social burdens. Developing targeted treatment strategies for URT infections that exhibit good biocompatibility, stability, and strong antimicrobial effects remains challenging. The dual antimicrobial and antiviral effects of iodine (I 2 ) in combination with the cooling sensation of l -menthol in the respiratory tract can simultaneously alleviate URT inflammation symptoms. However, as both I 2 and l -menthol are volatile, addressing stability issues is crucial. In this study, a potassium iodide β-cyclodextrin metal–organic framework [β-CD-POF(I)] with appropriate particle size was used to coload and deliver I 2 and l -menthol. Primarily, β-CD-POF(I) was employed as the most efficient carrier to significantly enhance the stability of I 2, surpassing any other known protection strategies in the pharmaceutical field (CD complexations, PVP conjugations, and cadexomer iodine). The mechanism underlying the improvement in stability of I 2 by β-CD-POF(I) was investigated through scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular docking. The results revealed that the key processes involved in improving stability were the inclusion of I 2 by β-CD cavities in β-CD-POF(I) and the formation of polyiodide anion between iodine ions and I 2 . Furthermore, the potential of β-CD-POF(I) to load and deliver drugs was validated, and coloading of l -menthol and I 2 demonstrated reliable stability. β-CD-POF(I) achieved a rate of URT deposition ≥95% in vitro, and the combined antibacterial effects of coloaded I 2 and l -menthol was better than I 2 or PVP-I alone, with no irritation noted following URT administration in rabbits. Therefore, the stable coloading of drugs by β-CD-POF(I), leading to enhanced antimicrobial effects, provides a new strategy for treating URT infections.