Tunable Temperature-Responsive Supramolecular Hydrogels Formed by Prodrugs As a Codelivery System

Taking advantage of the strong hydrophobicity of the anticancer drug camptothecin (CPT), the CPT molecule was conjugated to a class of low-molecular-weight (MW) poly(ethylene glycol) (PEG) chains (MW = 500, 1000, and 2000), forming an amphiphilic prodrug. The CPT-PEG prodrug formed stable hydrogels based on a combination of the partial inclusion complexation between one end of the PEG blocks and alpha-CD and the hydrophobic aggregation of CPT groups. Meanwhile, the formed hydrogels could be loaded with water-soluble drug 5-fluorouracil (5-FU), which is always combined with CPT drugs to enhance their anticancer activity. Moreover, the hydrogel systems demonstrate unique structure-related reversible gel-sol transition properties at a certain temperature due to the reversible supramolecular assembly, and the gel-sol transition temperature could be modulated by varying the length of the PEG chain and the concentrations of alpha-CD, demonstrating the possibility of achieving on-demand gel-sol transitions. The structure-related reversible gel-sol transition properties were proved by theological property, XRD, DSC, and SEM measurements. The different controlled release profiles of two different anticancer drugs showed significant temperature-dependent properties. This easily prepared supramolecular hydrogel with excellent biocompatibility and tunable temperature responsiveness has significant potential for controlled drug release applications.