Biomedical engineering approaches to enhance therapeutic delivery for malignant glioma

McCrorie, Phoebe; Vasey, Catherine E.; Smith, Stuart; Marlow, Maria; Alexander, Cameron; Rahman, Ruman

doi:10.1016/j.jconrel.2020.11.022

Cited by 33 publications

(34 citation statements)

References 132 publications

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“…Nanomedicine and therapeutics must be able to penetrate within the brain microenvironment to reach infiltrative cells that cause tumor recurrence and to provide more uniform drug distribution within tumors [10,11]. Therefore, in the last several years, many works have focused their attention on exploring new polymeric nanomedicines (using polymer nanoparticles, hydrogels, fibers, sprays) that could bypass Gliadel's drawbacks and allow therapeutics' diffusion in the GBM by active and passive targeting, achieving high local doses and improving survival [12].…”

Section: Introductionmentioning

confidence: 99%

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Malfanti¹,

Catania²,

Degros³

et al. 2022

Pharmaceutics

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Glioblastoma is an unmet clinical need. Local treatment strategies offer advantages, such as the possibility to bypass the blood–brain barrier, achieving high drug concentrations at the glioblastoma site, and consequently reducing systemic toxicity. In this study, we evaluated the feasibility of using hyaluronic acid (HA) for the local treatment of glioblastoma. HA was conjugated to doxorubicin (DOX) with distinct bio-responsive linkers (direct amide conjugation HA-NH-DOX), direct hydrazone conjugation (HA-Hz-DOX), and adipic hydrazone (HA-AdpHz-DOX). All HA-DOX conjugates displayed a small size (less than 30 nm), suitable for brain diffusion. HA-Hz-DOX showed the best performance in killing GBM cells in both 2D and 3D in vitro models and displayed superior activity in a subcutaneous GL261 tumor model in vivo compared to free DOX and other HA-DOX conjugates. Altogether, these results demonstrate the feasibility of HA as a polymeric platform for the local treatment of glioblastoma and the importance of rationally designing conjugates.

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Section: Introductionmentioning

confidence: 99%

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Malfanti¹,

Catania²,

Degros³

et al. 2022

Pharmaceutics

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“…The attraction of nanotechnology for intra-arterial drug delivery is multifold. Various authors noted these small particles could not only be loaded with different therapies, including small-molecule inhibitors, gene therapies or siRNAs, but could also be modified to cross the BBB through a variety of transport mechanisms and remain at the target site for longer periods of time to allow for a gradual release of loaded therapeutics [23,[105][106][107][108][109][110][111][112][113].…”

Section: Discussionmentioning

confidence: 99%

Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

2021

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Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.

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“…In addition to the aforementioned needed improvement in preclinical models that better reflect postsurgical residual disease, an important factor alongside the development of such multimodal strategies will be further improvements in the efficient delivery of therapeutically active doses of drugs beyond the BBB, which remains a significant challenge in glioblastoma therapy [ 3 ]. Potential innovations on the horizon include the use of MRI‐directed magnetic nanoparticles [ 217 , 218 ], surgical delivery of in situ gelling agents [ 219 , 220 ] and enhanced intrathecal/cerebrospinal fluid delivery using novel viral vectors, antibody ligands or exosomes [ 221 , 222 , 223 ]. Such approaches, in addition to traditional oral or intravenous delivery approaches, coupled with novel ways to disrupt the BBB, such as ultrasound [ 224 , 225 ] or TTFields [ 226 ]‐based approaches, will hopefully provide the best chance for DDR‐targeting approaches to provide much‐needed clinical benefit to patients and families faced with the devastating diagnosis of a high‐grade glioma.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

DDRugging glioblastoma: understanding and targeting the DNA damage response to improve future therapies

Rominiyi

Collis

2021

Molecular Oncology

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Glioblastoma is the most frequently diagnosed type of primary brain tumour in adults.These aggressive tumours are characterised by inherent treatment resistance and disease progression, contributing to ~190,000 brain-tumour related deaths globally each year. Current therapeutic interventions consist of surgical resection followed by radiotherapy and temozolomide chemotherapy, but average survival is typically around 1 year, with less than 10% of patients surviving more than 5 years. Recently, a fourth treatment modality of intermediate-frequency low-intensity electric fields [called tumourtreating fields ( TTFields)] was clinically approved for glioblastoma in some countries after it was found to increase median overall survival rates by ~5 months in a phase III randomised clinical trial. However, beyond these treatments, attempts to establish more effective therapies have yielded little improvement in survival for patients over the last 50 years. This is in contrast to many other types of cancer and highlights glioblastoma as a recognised tumour of unmet clinical need. Previous work has revealed that glioblastomas contain stem-cell-like subpopulations that exhibit heightened expression of DNA damage

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Biomedical engineering approaches to enhance therapeutic delivery for malignant glioma

Cited by 33 publications

References 132 publications

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

DDRugging glioblastoma: understanding and targeting the DNA damage response to improve future therapies

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