Self-Assembly of Succinated Paclitaxel into Supramolecular Hydrogel for Local Cancer Chemotherapy.

In the present study, we reported the generation of a molecular hydrogel of succinated paclitaxel (PTX-SA) by a self-hydrolytic strategy for potential local cancer chemotherapy. Upon self-hydrolysis of the ester bond of PTX-SA in phosphate-buffered saline (pH = 7.4) for 24 h, a PTX-SA supramolecular hydrogel formed spontaneously with a minimal gelation concentration of 0.25 wt%. The formed PTX-SA supramolecular hydrogel displayed a filamentous nanostructure, the nanofibers of which were typically several micrometers in length with a diameter of 10-15 nm. Rheological analysis suggested that the PTX-SA supramolecular hydrogel exhibited dominant elastic and thixotropic properties. Ionization of the carboxylate group together with the self-hydrolysis of the ester bond in PTX-SA are the major driving forces for the hydrogelation, as indicated by Fourier transform infrared spectroscopy (FTIR) analysis. The bioactive drug payload sustainably released from the supramolecular hydrogel over a period of 15 day in an in vitro release study, and the drug-release behavior could be finely controlled by altering the initial PTX-SA concentration. More importantly, the formed PTX-SA supramolecular hydrogel without compromising its pharmacological activity could efficiently inhibit the proliferation of cancer cells (HepG2 and MCF-7 cells) in vitro. Therefore, the generated PTX-SA supramolecular hydrogel might provide great potential as a novel drug-delivery system for local anti-cancer therapy.