Post-resection treatment of glioblastoma with an injectable nanomedicine-loaded photopolymerizable hydrogel induces long-term survival

Zhao, Mengnan; Danhier, Fabienne; Bastiancich, Chiara; Joudiou, Nicolas; Ganipineni, Lakshmi Pallavi; Tsakiris, Nikolaos; Gallez, Bernard; Rieux, Anne des; Jankovski, Aleksandar; Bianco, John; Préat, Véronique

doi:10.1016/j.ijpharm.2018.07.033

Cited by 58 publications

(49 citation statements)

References 42 publications

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“…There are some potential candidates that, combined with other materials, could lead to this goal. For instance, injectable hydrogels 33 , 34 are being studied as treatments for glioblastoma post resection. At the same time, these injectable materials offer the possibility of delivering drugs in a sustained release manner 35 , 36 .…”

Section: A More Exhaustive Multi-scale Designmentioning

confidence: 99%

Towards brain-tissue-like biomaterials

et al. 2020

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Section: A More Exhaustive Multi-scale Designmentioning

confidence: 99%

Towards brain-tissue-like biomaterials

et al. 2020

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“…It is important to note that the clinical success of Gliadel not only provides a rationale for this delivery mode, but that such significant efficacy (albeit modest), has not been reported for any molecular targeted monotherapy trialed for GBM. Indeed, there has been a resurgence of efficacious intracavity delivery of repurposed agents using biomaterials in preclinical orthotopic brain tumor models (43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Overall Survival in Malignant Glioma Is Significantly Prolonged by Neurosurgical Delivery of Etoposide and Temozolomide from a Thermo-Responsive Biodegradable Paste

Smith

Tyler

Gould

et al. 2019

Clinical Cancer Research

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Purpose: High-grade glioma (HGG) treatment is limited by the inability of otherwise potentially efficacious drugs to penetrate the blood-brain barrier. We evaluate the unique intracavity delivery mode and translational potential of a blend of poly(DL-lactic acid-co-glycolic acid; PLGA) and poly(ethylene glycol; PEG) paste combining temozolomide and etoposide to treat surgically resected HGG. Experimental Design: To prolong stability of temozolomide prodrug, combined in vitro drug release was quantitatively assessed from low pH-based PLGA/PEG using advanced analytic methods. In vitro cytotoxicity was measured against a panel of HGG cell lines and patient-derived cultures using metabolic assays. In vivo safety and efficacy was evaluated using orthotopic 9L gliosarcoma allografts, previously utilized preclinically to develop Gliadel. Results: Combined etoposide and temozolomide in vitro release (22 and 7 days, respectively) was achieved from a lactic acid-based PLGA/PEG paste, used to enhance stability of temozolomide prodrug. HGG cells from central-enhanced regions were more sensitive to each compound relative to primary lines derived from the HGG-invasive margin. Both drugs retained cytotoxic capability upon release from PLGA/ PEG. In vivo studies revealed a significant overall survival benefit in postsurgery 9L orthotopic gliosarcomas, treated with intracavity delivered PLGA/PEG/temozolomide/etoposide and enhanced with adjuvant radiotherapy. Long-term survivorship was observed in over half the animals with histologic confirmation of disease-free brain. Conclusions: The significant survival benefit of intracavity chemotherapy demonstrates clinical applicability of PLGA/ PEG paste-mediated delivery of temozolomide and etoposide adjuvant to radiotherapy. PLGA/PEG paste offers a future platform for combination delivery of molecular targeted compounds.

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“…This approach was investigated in the treatment of glioblastoma, employing a system based on polyethylene glycol dimethacrylate (PEGDMA). The photopolymerizable monomer was UV-irradiated in the brain tumor resection bed and employed for the delivery of Temozolomide (TMZ) and Paclitaxel (PTX) [132,133]. This approach could present several advantages, including the killing of the tumor cells that, after the resection of the main primary tumor, could infiltrate the brain tissue and the parenchyma.…”

Section: Synthetic Injectable Hydrogelsmentioning

confidence: 99%

Injectable Hydrogels for Cancer Therapy over the Last Decade

et al. 2019

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The interest in injectable hydrogels for cancer treatment has been significantly growing over the last decade, due to the availability of a wide range of starting polymer structures with tailored features and high chemical versatility. Many research groups are working on the development of highly engineered injectable delivery vehicle systems suitable for combined chemo-and radio-therapy, as well as thermal and photo-thermal ablation, with the aim of finding out effective solutions to overcome the current obstacles of conventional therapeutic protocols. Within this work, we have reviewed and discussed the most recent injectable hydrogel systems, focusing on the structure and properties of the starting polymers, which are mainly classified into natural or synthetic sources. Moreover, mapping the research landscape of the fabrication strategies, the main outcome of each system is discussed in light of possible clinical applications.

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Post-resection treatment of glioblastoma with an injectable nanomedicine-loaded photopolymerizable hydrogel induces long-term survival

Cited by 58 publications

References 42 publications

Towards brain-tissue-like biomaterials

Towards brain-tissue-like biomaterials

Overall Survival in Malignant Glioma Is Significantly Prolonged by Neurosurgical Delivery of Etoposide and Temozolomide from a Thermo-Responsive Biodegradable Paste

Injectable Hydrogels for Cancer Therapy over the Last Decade

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