Synthesis of an ursolic acid organic salt based low-molecular-weight supramolecular hydrogel with unique thermo-responsiveness behavior

Abstract

Low-molecular-weight supramolecular hydrogels (LMWSHs) are widely used in biomedical area and soft materials with desirable stimuli-responsiveness and self-healing abilities. Natural product hydrogelators (NPHGs) based LMWSHs can be synergistically used as drug matrix due to the low toxicity, good biocompatibility, biodegradability and biological activity from hydrogelator. Usually NPHGs based LMWSHs are obtained in organic reagents or following complex modifications. This work introduces a pentacyclic triterpene acid, ursolic acid, derivatives based LMWSH that formed in aqueous solution following simple preparation of 1-ethyl-3-methylimidazolium ursolic salt ([EMIM][UA]). Surprisingly, the gelator [EMIM][UA] based LMWSH showed unusual heating-induced irreversible transparent-turbid transitions in sol state at the gelator concentration lower than the minimum gelation concentration (MGC), but self-assembled to form LMWSH upon cooling like a conventional low-molecular-weight gelator (LMWG) at the gelator concentration higher than MGC. Rarely observed in the LMWSH system, a large number of crystallites were formed in both sol and gel state by increasing temperature, which was analogous to lower critical solution temperature (LCST) phase behavior in polymer systems. Moreover, the formed LMWSH displayed enormous viscoelasticity as chewing gum at room temperature with a porous honeycomb structure based supramolecular network. The good stability and injectability of the formed LMWSH, together with the in vitro drug releasing ability, demonstrated the potential of the formed LMWSH to be the drug delivery system for sustained drug releasing.