Abstract
Local drug delivery offers a means of achieving a high concentration of therapeutic agents directly at the tumor site, whilst minimizing systemic toxicity. For heterogenous cancers such as glioblastoma, multimodal therapeutic approaches hold promise for better efficacy. Herein, we aimed to create a well-defined and reproducible drug delivery system that also incorporates gold nanorods for photothermal therapy. Solvent-assisted micromolding was used to create uniform sacrificial templates in which microscale hydrogels were formed with and without gold nanorods throughout their structure. The microscale hydrogels could be loaded with doxorubicin, releasing it over a period of one week, causing toxicity to glioma cells. Since these microscale hydrogels were designed for direct intratumoral injection, therefore bypassing the blood–brain barrier, the highly potent breast cancer therapeutic doxorubicin was repurposed for use in this study. By contrast, the unloaded hydrogels were well tolerated, without decreasing cell viability. Irradiation with near-infrared light caused heating of the hydrogels, showing that if concentrated at an injection site, these hydrogels maybe able to cause anticancer activity through two separate mechanisms.
Highlights
Introduction iationsA broad range of biomaterials are being developed for local delivery of therapeutics to the required site in the body [1]
Polystyrene templates with block-shaped micro-structured cavities were produced by solvent-assisted microcontact molding using PDMS stamps that were created from two different silicon masters
We have developed a polyethylene glycol diacrylate hydrogel drug delivery system that was well defined in terms of dimensions, chemical composition, and drug release profile
Summary
A broad range of biomaterials are being developed for local delivery of therapeutics to the required site in the body [1]. For brain cancers such as high-grade gliomas, in particular glioblastoma, whose prognosis can be very poor, locally administered therapeutics may offer improved outcomes over the current treatment strategy [2]. The potential advantages of using drug delivery systems to release the drug at the tumor site (or in the tumor resection cavity following cytoreductive resection) include raising the local dose of the drug at the tumor site and repurposing drugs that cannot pass the blood–brain barrier. Local drug delivery gives the opportunity to use drugs such as doxorubicin (which exhibits greater cytotoxicity to glioblastoma cells than the currently clinically used temozolomide) for combinatory approaches aiming at bypassing cancer cells chemoresistance [3].
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