An injectable in situ hydrogel platform for sustained drug release against Glioblastoma

Abstract

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Despite aggressive surgical and medical treatments, the prognosis for patients with GBM remains grim and tumor recurrence is inevitable. Long-acting localized chemotherapy can not only reduce systemic toxicity, but also maintain chemotherapeutic concentration at the tumor sites over prolonged duration, thereby having the potential to improve GBM treatment. The present research aims to investigate an injectable in situ hydrogel made up of biopolymers collagen and hyaluronic acid that are abundant in the brain for sustained chemotherapy against GBM. Temozolomide (TMZ), an alkylating antineoplastic agent and the first-line treatment for GBM, was selected as the model chemotherapeutic and encapsulated in liposomes to facilitate deep tumor penetration. Whether the presence of liposomes affected gelling behavior and rheological properties of the collagen-based hydrogel system was investigated. Moreover, the in vitro efficacy of the TMZ-liposome/hydrogel composite was studied using a 3D spheroid GBM model. The developed TMZ-liposome/hydrogel composite gelled within 1 min at 37 °C and demonstrated sustained payload release and deep tumor penetration in the 3D GBM spheroids. More importantly, the composite remarkably inhibited glioma cell growth. These results showed that the developed liposome/in situ hydrogel composite is a promising drug delivery platform for the long-term localized treatment of GBM.