Development of a gastrointestinal-restricted cellulose-based copper sequestrant: potential application in treating Wilson's disease

Wilson's disease is a type of neurogenetic disease associated with a disorder of copper metabolism. In general, de‑coppering drugs such as copper chelators and zinc preparations are used to treat this condition. However, the effects of zinc preparations are slow, and long-term use of copper chelators results in some adverse reactions (e.g., nephrotoxicity). In this study, we developed a novel modified microcrystalline cellulose-based adsorbent (MCC-NS) as a gastrointestinal-restricted sequestrant to remove excess copper from the body. Scanning electron microscopy and X-ray photoelectron spectroscopy were performed to characterize the resulting adsorbent (also called de‑coppering cellulose). These methods revealed the successful immobilization of amino and sulfhydryl groups on the surface of MCC. In addition, de‑coppering performance tests revealed the high copper affinity of MCC-NS. This adsorbent removes excess serum copper in a timely manner in Cu-overdosed mice and can reduce copper deposition in tx-j mice, thereby alleviating liver damage. In vivo biosafety evaluation experiments revealed that long-term MCC-NS administration did not injure the primary organs of the mice. Collectively, our findings suggest the potential of as-prepared de‑coppering cellulose as an oral gastrointestinal-restricted copper sequestrant for treating Wilson's disease with few adverse reactions.