An adherent tissue-inspired hydrogel delivery vehicle utilised in primary human glioma models

Rowland, Matthew; Parkins, Christopher C.; McAbee, Joseph H.; Kolb, Anna; Hein, Robert; Loh, Xian Jun; Watts, Colin; Scherman, Oren A.

doi:10.1016/j.biomaterials.2018.05.054

Cited by 77 publications

(72 citation statements)

References 43 publications

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“…Although the kinetics of chemotherapy release may be comparable, hydrogels do not last long enough in the resection cavity (nor are stiff enough) to cause the same adverse effects as wafers. Promising examples of rapidly biodegradable hydrogels include supramolecular or physically assembled hydrogels for parenteral drug delivery applications . For example, we previously reported physical hydrogels for local GB drug delivery that self‐assemble via host–guest interactions .…”

Section: Promising Soft Materials For Local Deliverymentioning

confidence: 99%

Designing Next‐Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic

Tabet

Jensen

Parkins

et al. 2019

Adv Healthcare Materials

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The clinical outcomes and 5-year survival rate for patients with glioblastoma (GB) make it among the most pernicious and challenging diseases to treat. Despite all the resources, time, and talent focused on developing targeted and/or local delivery technologies by the biomaterials community for GB, the clinical performance of the FDA-approved therapy carmustine ((BCNU)-loaded polyanhydride wafers) and clinical trials of other material approaches have been discouraging. As disappointing is the remarkably stagnant clinical translation of next-generation material approaches for GB. Despite encouraging preclinical results from hydrogels and modified wafer formulations loaded with more efficacious chemotherapies, a total of zero have completed even a phase I clinical trial. Other strategies, including convection-enhanced delivery, microsphere formulations, or drug-loaded nanoparticles have seen limited, albeit some, translation into the clinic with mixed results. This lackluster progress can be attributed, in part, to the paucity of communication between material scientists, biomedical scientists, and clinicians. When examining the purported clinical relevance of embedding certain material properties into formulations, it is clear that some widely known truths about the nature of GB progression among clinicians have not reached the biomaterials community.Furthermore, a closer examination of the lessons from the BCNU wafers and other clinical trials of GB drug delivery materials may enrich and inspire materials scientists to create new systems that satisfy unmet medical needs identified by the clinical community. In tandem, clinicians and biomedical scientists may benefit from a short review highlighting the biocompatibility, safety, longevity, kinetics, tunability, and efficacy of promising new drug delivery materials without inundation by chemical and physical characterizations or discussions.Another key challenge in treating GB is an incomplete understanding of disease pathophysiology, such as mechanisms driving intrinsic and adaptive GB cell chemoresistance. A combined approach where biomedical scientists and material To date, the clinical outcomes and survival rates for patients with glioblastoma (GB) remain poor. A promising approach to disease-modification involves local delivery of adjuvant chemotherapy into the resection cavity, thus circumventing the restrictions imposed by the blood-brain barrier. The clinical performance of the only FDA-approved local therapy for GB [carmustine (BCNU)-loaded polyanhydride wafers], however, has been disappointing. There is an unmet medical need in the local treatment of GB for drug delivery vehicles that provide sustained local release of small molecules and combination drugs over several months. Herein, key quantitative lessons from the use of local and systemic adjuvant chemotherapy for GB in the clinic are outlined, and it is discussed how these can inform the development of next-generation therapies. Several recent approaches are highlighted, and it is proposed that long...

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Section: Promising Soft Materials For Local Deliverymentioning

confidence: 99%

Designing Next‐Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic

Tabet

Jensen

Parkins

et al. 2019

Adv Healthcare Materials

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“…To address these limitations, drug releasing implants are being developed, most often composed of biodegradable polymers, that may provide improved local delivery of promising chemotherapeutics in the CNS [11]. While multiple studies have evaluated the ability of different carriers to deliver chemotherapeutic payloads to glioblastoma cells, the majority of these studies have tested them in sub-optimal conditions using either in vitro [12] or subcutaneous flank environments [13], or testing them on suboptimal, multi-passaged glioma cell lines that often do not recapitulate the migratory capacity of patient tumors [14] [15] [16]. Fully understanding the potential of these vehicles requires testing in realistic in vivo environments.…”

Section: Introductionmentioning

confidence: 99%

Injectable diblock copolypeptide hydrogel provides platform to maintain high local concentrations of taxol and local tumor control

Garrett¹,

O’Shea

Wollenberg

et al. 2019

Preprint

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Introduction: Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.Methods: The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells.Results: The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model, of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to a high local concentration of paclitaxel and led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment.Conclusions: These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.

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“…These materials exhibit an observable change in their properties upon exposure to the stimulus. Such changes include modification of their shape, solubility, surface characteristics, and the ability to self‐assemble or sol‐to‐gel transition …”

Section: Introductionmentioning

confidence: 99%

Biodegradable Thermogelling Polymers

Loh

Chee

2018

Small Methods

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Thermogelling materials are envisioned as smart biomaterials with significant potential in the biomedical field. Their importance lies at the intersection between two highly medically relevant classes of materials: hydrogels and smart materials. They possess high water content and tunable properties of hydrogels and the ability to respond to external temperature variations with a simple, physical, and reversible sol‐to‐gel phase transition. Thermogels are proposed for many uses including drug delivery, gene delivery, and scaffolding for tissue engineering. Recent developments of biodegradable thermogelling polymers are reviewed, focusing on the properties of different thermogel systems and how those properties correlate with biomaterials behavior with the goal of providing safe and effective treatment for the treatment of diseases such as diabetes, glaucoma, and cancer.

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An adherent tissue-inspired hydrogel delivery vehicle utilised in primary human glioma models

Cited by 77 publications

References 43 publications

Designing Next‐Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic

Designing Next‐Generation Local Drug Delivery Vehicles for Glioblastoma Adjuvant Chemotherapy: Lessons from the Clinic

Injectable diblock copolypeptide hydrogel provides platform to maintain high local concentrations of taxol and local tumor control

Biodegradable Thermogelling Polymers

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