Injectable nanomedicine hydrogel for local chemotherapy of glioblastoma after surgical resection

Bastiancich, Chiara; Bianco, John; Vanvarenberg, Kévin; Ucakar, Bernard; Joudiou, Nicolas; Gallez, Bernard; Bastiat, Guillaume; Lagarce, Frédéric; Préat, Véronique; Danhier, Fabienne

doi:10.1016/j.jconrel.2017.08.019

Cited by 113 publications

(66 citation statements)

References 55 publications

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“…The primary disadvantage of these hydrogels is the foreign body response, which eventually leads to isolation of the implant through formation of a fibrous capsule that can induce patient discomfort and disruption of nanocarrier release kinetics 23 , 25 . To enhance tolerability of nanocarrier-loaded hydrogels, alternative strategies have emerged that include hydrogels composed of non-covalently linked nanocarriers themselves without polymer matrices 26 , as well as hydrogels composed of polymers with reduced inflammatory potential 24 , 27 . We sought to combine and improve upon both these strategies by developing a synthetic macromolecular hydrogel network that could dynamically restructure into monodisperse nanoscale vehicles for non-inflammatory bioresporption and sustained nanocarrier delivery.…”

Section: Introductionmentioning

confidence: 99%

Sustained micellar delivery via inducible transitions in nanostructure morphology

et al. 2018

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Nanocarrier administration has primarily been restricted to intermittent bolus injections with limited available options for sustained delivery in vivo. Here, we demonstrate that cylinder-to-sphere transitions of self-assembled filomicelle (FM) scaffolds can be employed for sustained delivery of monodisperse micellar nanocarriers with improved bioresorptive capacity and modularity for customization. Modular assembly of FMs from diverse block copolymer (BCP) chemistries allows in situ gelation into hydrogel scaffolds following subcutaneous injection into mice. Upon photo-oxidation or physiological oxidation, molecular payloads within FMs transfer to micellar vehicles during the morphological transition, as verified in vitro by electron microscopy and in vivo by flow cytometry. FMs composed of multiple distinct BCP fluorescent conjugates permit multimodal analysis of the scaffold’s non-inflammatory bioresorption and micellar delivery to immune cell populations for one month. These scaffolds exhibit highly efficient bioresorption wherein all components participate in retention and transport of therapeutics, presenting previously unexplored mechanisms for controlled nanocarrier delivery.

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Section: Introductionmentioning

confidence: 99%

Sustained micellar delivery via inducible transitions in nanostructure morphology

et al. 2018

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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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“…[ 61 ] Another intratumoral drug delivery system, described by Bastianchich et al., consists of lipid nanocapsule (LNC) hydrogels comprised of the chemotherapy drug Germcitabine (GemC 12 ) with lauroyl surfactant (GemC 12 ‐LNCs) ( Figure a). [ 62 ] This antitumor strategy significantly increased mouse survival compared to untreated controls (Figure 4b,c). Additionally, when injected in the surgical cavity postresection, GemC 12 ‐LNC hydrogel delayed tumor recurrence (Figure 4d).…”

Section: Pillars Of Gbm Treatment Improved By Injectable Biomaterialsmentioning

confidence: 94%

Injectable Biomaterials for Treatment of Glioblastoma

Anderson

Segura

2020

Adv Materials Inter

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Injectable nanomedicine hydrogel for local chemotherapy of glioblastoma after surgical resection

Cited by 113 publications

References 55 publications

Sustained micellar delivery via inducible transitions in nanostructure morphology

Sustained micellar delivery via inducible transitions in nanostructure morphology

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

Injectable Biomaterials for Treatment of Glioblastoma

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