Porous organic polymers based on deep-cavity calixarene for broad-spectrum and high-affinity drug adsorption in gastrointestinal tract

Abstract

Gastrointestinal adsorption of drugs holds significant clinical value for mitigating local side effects in the digestive tract and enabling immediate intervention in cases of drug overdose. However, the complex gastrointestinal environment presents considerable challenges to the affinity and anti-interference capabilities of adsorbents. Macrocyclic hosts, renowned for their exceptional host–guest recognition properties, offer a promising strategy to overcome these challenges. In this study, a series of C=C-linked calixarene-based porous organic polymers were synthesized via Knoevenagel condensation. The stable C=C bonds not only enhance the structural stability of the material but also extend the calixarene's cavity longitudinally through conjugation, thereby significantly improving its affinity for drug molecules. Experimental results demonstrate that, under simulated complex gastrointestinal fluid conditions, the prepared calixarene-based polymers exhibit broad-spectrum and highly efficient adsorption performance toward various chemotherapeutic and antidepressant drugs. Notably, our adsorbent demonstrated affinity superior to the best-reported literature values for 9 of the 12 drugs with existing data. Further in vivo experiments demonstrate their superior biological safety and remarkable therapeutic efficacy in preventing chemotherapy-induced mucositis.