Lauroyl-gemcitabine lipid nanocapsule hydrogel for the local treatment of glioblastoma

authors

• Bastiancich Chiara

keywords

• Glioblastoma
• Local delivery
• Nanomedicine
• Hydrogels
• Preclinical models

abstract

Glioblastoma (GBM) is an aggressive malignant brain tumor characterized by rapid proliferation and propensity to infiltrate healthy brain tissue. Despite aggressive standard of care therapy GBM always recur, mainly because of its high invasiveness and chemoresistance to alkylating drugs. In this Thesis, we evaluate the feasibility, efficacy and safety of the nanomedicine hydrogel Lauroyl-gemcitabine lipid nanocapsule (GemC12-LNC) for the local treatment of GBM. GemC12-LNC was prepared by a phase-inversion technique process. It is injectable, adapted for brain implantation and able to sustainably release the drug in vitro. In healthy mice brain, no inflammation, apoptosis or microglia activation was observed after exposure to the hydrogel suggesting that this system is well tolerated and suitable for an application in the brain. Intratumoral injection of GemC12-LNC hydrogel in a U87subcutaneous and orthotopic GBM model significantly reduced tumor growth and increased the animal’s median survival compared to the controls, respectively. Moreover, to mimic the clinical setting, a reproducible tumor resection technique of U87 GBM and 9L gliosarcoma was developed and the GemC12-LNC hydrogel slowed down the formation of recurrences in mice and rats brain, respectively. In conclusion, the feasibility efficacy and safety of GemC12-LNC have been shown in vitro and in several preclinical in vivo models showing that this nanomedicine hydrogel is a promising and innovative delivery system for the local treatment of GBM. This gel can be directly injected in the GBM resection cavity, has a very simple formulation and combines the properties of nanomedicines and hydrogels.

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