Localized therapy of the highly malignant brain tumor glioblastoma multiforme (GBM) could help to drastically improve the treatment efficiency and increase the patient's median survival. Here, a macroscopic PDMS matrix composed of interconnected microchannels for tailored drug release and localized GBM therapy is introduced. Based on a simple bottom-up fabrication method using a highly versatile sacrificial template, the presented strategy solves the scaling problem associated with the previously developed microchannel-based drug delivery systems, which were limited to two dimensions due to the commonly employed top-down microfabrication methods. Additionally, tailoring of the microchannel density, the fraction of drug-releasing microchannels and the macroscopic size of the drug delivery systems enabled precise adjustment of the drug release kinetics for more than 10 days. As demonstrated in a long-term GBM in vitro model, the release kinetics of the exemplarily chosen GBM drug AT101 could be tailored by variation of the microchannel density and the initial drug concentration, leading to diffusion-controlled AT101 release. Adapting a previously developed GBM treatment plan based on a sequential stimulation with AT101, measured anti-tumorigenic effects of free versus PDMS-released AT101 were comparable in human GBM cells and demonstrated efficient biological activity of PDMS-released AT101.
Keywords: PDMS; glioblastoma; local drug delivery; localized therapy; microchannels.