Drug combination using an injectable nanomedicine hydrogel for glioblastoma treatment

Abstract

Lauroyl-gemcitabine lipid nanocapsules (GemC12-LNC) hydrogel, administered intratumorally or perisurgically in the tumor resection cavity, increases animal survival in several orthotopic GBM models. We hypothesized that GemC12-LNC can be used as nanodelivery platform for other drugs, to obtain a combined local therapeutic approach for GBM. Paclitaxel (PTX) was selected as a model molecule and PTX-GemC12-LNC formulation was evaluated in terms of physicochemical and mechanical properties. The PTX-GemC12-LNC hydrogel stability and drug release were evaluated over time showing no significant differences compared to GemC12-LNC. The drug combination was evaluated on several GBM cell lines showing increased cytotoxic activity compared to the original formulation and synergy between PTX and GemC12. Our results suggest that GemC12-LNC hydrogel can be used as nanodelivery platform for dual drug delivery to encapsulate active agents with different mechanisms of action to achieve a better antitumor efficacy against GBM or other solid tumors