Glioblastoma is an aggressive and often fatal brain cancer. Despite significant progress in cancer treatment, glioblastoma remains one of the least curable forms of cancer, with a 5-year survival rate of only 5%. The current standard of care, known as the Stupp’s protocol, has not seen substantial improvements in over two decades and is associated with various therapy-induced complications The unique characteristics of glioblastoma, such as the presence of the blood-brain barrier and the thick extracellular matrix, as well as its biological heterogeneity, pose significant hurdles to effective treatment. These factors limit the delivery and distribution of therapeutic agents to the tumor site and contribute to the rapid recurrence of the disease. Therefore, the development of innovative drug delivery systems for local and regional therapies is of utmost importance. A new study conducted by Italian Institute of Technology scientists: Dr. Daniele Di Mascolo, Dr. Irene Guerriero, Dr. Cristiano Pesce, Dr. Raffaele Spanò, Dr. Anna Lisa Palange, and led by Dr. Paolo Decuzzi, introduced a promising approach in addressing the formidable challenge of treating glioblastoma. The research work is now published in the Journal ACS Nano. The authors developed μMESH, a mechanically conformable, biodegradable implant designed to address these challenges. μMESH consists of a polyvinyl alcohol (PVA) microlayer supporting a poly(lactic-co-glycolic acid) (PLGA) micronetwork. It offers precise control over its geometrical attributes, allowing for customization based on specific therapeutic requirements. Importantly, μMESH can carry a variety of therapeutic agents, including hydrophobic and water-soluble drugs.
The researchers evaluated four different μMESH configurations, each loaded with highly potent cytotoxic molecules, docetaxel (DTXL), and paclitaxel (PTXL), either in their native molecular form or as nanomedicines encapsulated within conventional spherical polymeric nanoparticles. The research conducted thorough physicochemical, pharmacological, and biological characterizations to optimize these μMESH-based formulations. One of the key findings of the study was the efficient loading of drugs into μMESH, with DTXL showing higher encapsulation efficiency than PTXL. This can be attributed to differences in drug solubility in the solvents used during device fabrication. The release profiles of these drugs from μMESH were also examined, with DTXL demonstrating a faster initial release rate compared to PTXL. This burst release is essential for targeting rapidly dividing malignant cells. Furthermore, the authors discussed the cytotoxicity of these drug-loaded μMESH configurations using both monolayer cultures and 3D tumor spheroids, which better mimic the in vivo tumor microenvironment. The results demonstrated the potency of DTXL over PTXL, consistent with existing knowledge. Importantly, μMESH loaded with DTXL was found to be as effective as free DTXL in inducing cell death in 3D tumor spheroids. These findings suggest that μMESH has the potential to enhance the therapeutic efficacy of these drugs.
The research team demonstrated preclinical validation in orthotopic murine models of glioblastoma. The results indicated that μMESH-based therapies significantly prolonged the survival of treated mice compared to untreated controls. Notably, μMESH loaded with DTXL demonstrated particularly promising outcomes, with a substantial portion of the mice surviving beyond the 3-month observation period. In conclusion, the study’s findings suggest that μMESH, a deformable and biodegradable implant, has the potential to address some of the challenges associated with glioblastoma treatment. Its ability to provide sustained drug release over an extended period, coupled with its customizable design, makes it a promising platform for localized and regional therapies. While further research is needed to validate these findings and explore potential clinical applications, this study represents a significant step toward improving the prognosis for glioblastoma patients. The development of innovative drug delivery systems like μMESH offers hope for better outcomes in the fight against this devastating disease.
Di Mascolo D, Guerriero I, Pesce C, Spanò R, Palange AL, Decuzzi P. μMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment. ACS Nano. 2023 Aug 8;17(15):14572-14585. doi: 10.1021/acsnano.3c01574.