Hydrogelation of TPGS for locoregional combination therapy of cancer

Abstract

D-ɑ-tocopheryl poly(ethylene glycol)1000 succinate (TPGS) has been extensively applied in drug delivery systems for its amphiphilic property and inherent bioactivity. But TPGS has not always been utilized solely for the unstability of TPGS micelle. Inspired by the hydrogels made from other amphiphilic molecules, thermosensitive TPGS hydrogels were firstly discovered and developed in the presence of specific anions, which self-assembled from the aggregation of TPGS micelles stimulated by heating and salting-out effect. Subsequently, hydrophobic doxorubicin (DOX) loaded TPGS micelles were likewise prepared and converted into DOX loaded hydrogel with the help of β-Glycerol phosphate disodium (β-GP). It was found that the amount of TPGS and β-GP in the solution considerably affected the gelation time and critical temperature. One of the formulations containing 4 wt% TPGS and 15 wt% β-GP was selected due to its appropriate gelation time and temperature for subcutaneously injection. Pristine and drug-loaded TPGS hydrogels were explored for their potential values in clinic applications. Derived from the bioactivity of TPGS, the pristine TPGS hydrogel exhibited a certain tumor inhibiting efficiency comparable to the DOX-containing formulations. And the efficiency of DOX-loaded TPGS hydrogels were dosage-dependent and superior to systemically administrated free DOX, which demonstrated a synergistic effect between DOX and TPGS hydrogel. In short, this study developed a multifunctional injectable hydrogel and provided a new synergetic strategy for tumor therapy.