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 (I2) in combination with the cooling sensation of l-menthol in the respiratory tract can simultaneously alleviate URT inflammation symptoms. However, as both I2 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 I2 and l-menthol. Primarily, β-CD-POF(I) was employed as the most efficient carrier to significantly enhance the stability of I2, 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 I2 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 I2 by β-CD cavities in β-CD-POF(I) and the formation of polyiodide anion between iodine ions and I2. Furthermore, the potential of β-CD-POF(I) to load and deliver drugs was validated, and coloading of l-menthol and I2 demonstrated reliable stability. β-CD-POF(I) achieved a rate of URT deposition ≥95% in vitro, and the combined antibacterial effects of coloaded I2 and l-menthol was better than I2 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.