Supramolecular hydrogel containing multi-generation poly(L-lysine) dendrons for sustained co-delivery of docetaxel and matrix metallopeptidase-9 short hairpin RNA plasmid

Abstract

To obtain an efficient drug and gene co-delivery hydrogel, methoxy polyethylene glycol was reacted with the caprolactone units to form the MPEG-PCL block copolymer through the polymerization reaction, which is amphiphilic and can load the hydrophobic drugs. Then, MPEG-PCL conjugated with a multi-generation poly(L-lysine) dendron to form the guest molecule MPEG-PCL-PLLD. After interacted with α-cyclodextrin through host–guest inclusion, the drug and gene dual carrier of supramolecular hydrogel was obtained. The physical properties of the hydrogel, such as the gelation time, the hydrogel strength, or its shear viscosity, could be modulated by the hose molecule of α-cyclodextrin content. MPEG-PCL-PLLD could co-load the drug and gene effectively. After gelation, the loaded drug and gene could be released sustainedly, and the release rate of them was also modulated by the α-cyclodextrin content. The supramolecular hydrogel showed a sustained effect on tumor cells and could induce the cell apoptosis sustainedly. Moreover, the co-delivery strategy was superior to only drug or gene used in tumor cell inhibition. This supramolecular hydrogel as the high-efficiency and sustained co-delivery system showed a promising application in a long-term tumor therapy.