Supramolecular hydrogel based on high-solid-content mPECT nanoparticles and cyclodextrins for local and sustained drug delivery.

A novel injectable and high-solid-content drug-loaded supramolecular hydrogel (PTX-mPECT NP/α-CDgel) was prepared by self-assembly of inclusion complexes based on PTX-loaded mPECT (methoxy poly(ethylene glycol)-b-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-un-decanone)) nanoparticles (PTX-mPECT NPs) and α-cyclodextrin (α-CD). Paclitaxel (PTX) was chosen as a hydrophobic drug encapsulated into mPECT NPs. Then, gelation occurred when the aqueous solution of α-CD was added to the PTX-mPECT NPs aqueous dispersion within several seconds after stirring. Importantly, with the erosion of the hydrogel, PTX-loaded NPs could be released again and then PTX released further. Rheological studies showed that PTX-mPECT NP/α-CDgel with good injectability underwent a shear-induced sol-gel transition. The results of in vitro drug-release studies demonstrated a sustained-release profile, and the cumulative release of PTX was ≈35% after 20 days. The results of cell-uptake studies and in vitro cytotoxicity studies indicated that the PTX-loaded NPs have been efficiently delivered to cells and killed tumor cells. Higher suppression of tumor growth demonstrated the remarkable anticancer effect of PTX-mPECT NP/α-CDgel upon peritumoral injection. These results showed that high-solid-content PTX-mPECT NP/α-CDgel based on in situ systems could be a promising candidate for local and sustained drug delivery.