A supramolecular formulation of icariin@sulfonatoazocalixarene for hypoxia-targeted osteoarthritis therapy

Osteoarthritis (OA) is the most prevalent joint disease and icariin is a promising drug for its treatment. However, the clinical use of icariin is hindered by poor water solubility, low bioavailability, and non-specific release and biological distribution. Herein, sulfonated azocalix[4]arene (SAC4A) with enhanced water solubility, recognition capacity, and designed responsiveness was used to improve the efficiency of icariin for OA therapy. SAC4A, a macrocycle with well-defined molecular weight and structure, could encapsulate and enhance water solubility of various drugs. In addition, SAC4A enables hypoxia-responsive release of loaded drug. Compared with icariin treatment, supramolecular complex icariin@SAC4A significantly relieved OA symptoms of rats, including more regular bone morphology and structure, and lower degree of cartilage damage. Moreover, the supramolecular formulation demonstrated various advantages, including easy preparation, hypoxia-triggered release, and small size that conducive to drug penetration.