Light-Activated Local Drug Delivery From Hydrogels: Potential for GBM Treatment

Abstract

Following post-operative treatment, the vast majority of GBMs recur, usually within 2 cm of the tumor resection margin. Since these tumors seldom metastasize outside the CNS, improved localized therapies should prove beneficial. Drug delivery systems (DDS) that allow control over drug release by an externally applied energy, such as light, have the potential of improving the results of chemotherapy. Light-activated hydrogel DDS, implanted in the operative cavity formed by tumor resection, bypasses the blood brain barrier and allows for a precise spatio-temporal control of drug release or drug activation. Localized, on-demand release of anticancer drugs to normal brain infiltrated by tumor cells should therefore improve therapeutic efficacy and minimize systemic, drug-related side effects. Various forms of light-activated hydrogels have utilized near infrared, visible or ultraviolet wavelength irradiation. One form of hydrogel, fibrin glue (FG), composed of a combination of fibrinogen and thrombin, has several characteristics that make it well-suited for this form of sustained release drug delivery. Unlike most synthetic hydrogels, FG is a natural product and has been used clinically in surgery for decades, so its biocompatibility and lack of toxicity has been clearly proven. The light-driven drug activation technology, photochemical internalization (PCI) has been shown to enhance the intracellular efficacy of chemotherapeutic agents released from fibrin glue. A summary of the light-activated hydrogel techniques developed for the site and temporal-specific delivery of chemotherapy for the treatment of GBM will be discussed in this review.