731 results match your criteria convection-enhanced delivery

A therapeutic convection-enhanced macroencapsulation device for enhancing β cell viability and insulin secretion.

Proc Natl Acad Sci U S A 2021 Sep;118(37)

Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Boston, MA 02115;

Islet transplantation for type 1 diabetes treatment has been limited by the need for lifelong immunosuppression regimens. This challenge has prompted the development of macroencapsulation devices (MEDs) to immunoprotect the transplanted islets. While promising, conventional MEDs are faced with insufficient transport of oxygen, glucose, and insulin because of the reliance on passive diffusion. Read More

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September 2021

On the microstructural origin of brain white matter hydraulic permeability.

Proc Natl Acad Sci U S A 2021 Sep;118(36)

Department of Mechanical Engineering, Imperial College London, London SW7 2AZ, United Kingdom;

Brain microstructure plays a key role in driving the transport of drug molecules directly administered to the brain tissue, as in Convection-Enhanced Delivery procedures. The proposed research analyzes the hydraulic permeability of two white matter (WM) areas (corpus callosum and fornix) whose three-dimensional microstructure was reconstructed starting from the acquisition of electron microscopy images. We cut the two volumes with 20 equally spaced planes distributed along two perpendicular directions, and, on each plane, we computed the corresponding permeability vector. Read More

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September 2021

An Update on Gene Therapy Approaches for Parkinson's Disease: Restoration of Dopaminergic Function.

J Parkinsons Dis 2021 Aug 4. Epub 2021 Aug 4.

Department of Neurological Surgery, Ohio State University College of Medicine, Columbus, OH, USA.

At present there is a significant unmet need for clinically available treatments for Parkinson's disease (PD) patients to stably restore balance to dopamine network function, leaving patients with inadequate management of symptoms as the disease progresses. Gene therapy is an attractive approach to impart a durable effect on neuronal function through introduction of genetic material to reestablish dopamine levels and/or functionally recover dopaminergic signaling by improving neuronal health. Ongoing clinical gene therapy trials in PD are focused on enzymatic enhancement of dopamine production and/or the restoration of the nigrostriatal pathway to improve dopaminergic network function. Read More

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Liposomal IR-780 as a Highly Stable Nanotheranostic Agent for Improved Photothermal/Photodynamic Therapy of Brain Tumors by Convection-Enhanced Delivery.

Cancers (Basel) 2021 Jul 22;13(15). Epub 2021 Jul 22.

Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan.

As a hydrophobic photosensitizer, IR-780 suffers from poor water solubility and low photostability under near infrared (NIR) light, which severely limits its use during successive NIR laser-assisted photothermal/photodynamic therapy (PTT/PDT). To solve this problem, we fabricate cationic IR-780-loaded liposomes (ILs) by entrapping IR-780 within the lipid bilayer of liposomes. We demonstrate enhanced photostability of IR-780 in ILs with well-preserved photothermal response after three repeated NIR laser exposures, in contrast to the rapid decomposition of free IR-780. Read More

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Intraarterial delivery of bevacizumab and cetuximab utilizing blood-brain barrier disruption in children with high-grade glioma and diffuse intrinsic pontine glioma: results of a phase I trial.

J Neurosurg Pediatr 2021 Aug 6:1-9. Epub 2021 Aug 6.

3Department of Neurosurgery, NewYork-Presbyterian Hospital-Weill Cornell Medicine, New York, New York; and.

Objective: Delivery of drugs intraarterially to brain tumors has been demonstrated in adults. In this study, the authors initiated a phase I trial of superselective intraarterial cerebral infusion (SIACI) of bevacizumab and cetuximab in pediatric patients with refractory high-grade glioma (diffuse intrinsic pontine glioma [DIPG] and glioblastoma) to determine the safety and efficacy in this population.

Methods: SIACI was used to deliver mannitol (12. Read More

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Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma.

Surg Neurol Int 2021 6;12:337. Epub 2021 Jul 6.

Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.

Background: Glioblastoma (GBM) is the most common malignant brain tumor and carries a dismal prognosis. Attempts to develop biologically targeted therapies are challenging as the blood-brain barrier can limit drugs from reaching their target when administered through conventional (intravenous or oral) routes. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. Read More

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Chemosensitization of Temozolomide-Resistant Pediatric Diffuse Midline Glioma Using Potent Nanoencapsulated Forms of a N(3)-Propargyl Analogue.

ACS Appl Mater Interfaces 2021 Aug 26;13(30):35266-35280. Epub 2021 Jul 26.

Translational Health Sciences, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom.

The lack of clinical response to the alkylating agent temozolomide (TMZ) in pediatric diffuse midline/intrinsic pontine glioma (DIPG) has been associated with -methylguanine-DNA-methyltransferase (MGMT) expression and mismatch repair deficiency. Hence, a potent N(3)-propargyl analogue (N3P) was derived, which not only evades MGMT but also remains effective in mismatch repair deficient cells. Due to the poor pharmacokinetic profile of N3P ( < 1 h) and to bypass the blood-brain barrier, we proposed convection enhanced delivery (CED) as a method of administration to decrease dose and systemic toxicity. Read More

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Antibody-drug conjugates for H3K27M-mutant diffuse midline gliomas: prospects and challenges.

Ther Deliv 2021 08 21;12(8):553-557. Epub 2021 Jul 21.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

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Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons.

Nat Commun 2021 07 12;12(1):4251. Epub 2021 Jul 12.

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder characterized by deficient synthesis of dopamine and serotonin. It presents in early infancy, and causes severe developmental disability and lifelong motor, behavioral, and autonomic symptoms including oculogyric crises (OGC), sleep disorder, and mood disturbance. We investigated the safety and efficacy of delivery of a viral vector expressing AADC (AAV2-hAADC) to the midbrain in children with AADC deficiency (ClinicalTrials. Read More

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Convection enhanced delivery of light responsive antigen capturing oxygen generators for chemo-phototherapy triggered adaptive immunity.

Biomaterials 2021 08 16;275:120974. Epub 2021 Jun 16.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore. Electronic address:

In recent years, combination therapy has emerged as the cornerstone of clinical practice in treating glioblastoma multiforme. However, their ability to trigger and leverage the body's adaptive immunity has rarely been studied. Tumour heterogeneity, the presence of the blood-brain barrier, and an immunosuppressive tumor microenvironment play a crucial role in the 90% local tumor recurrence post-treatment. Read More

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[Chemotherapy for Glioma].

Ryuta Saito

No Shinkei Geka 2021 May;49(3):588-596

Department of Neurosurgery, Nagoya University, Graduate School of Medicine.

Chemotherapeutic treatment of malignant gliomas is extremely challenging. Tumor accumulation of systemically-administrated chemotherapy is always hindered by the blood-brain barrier(BBB). Although temozolomide administered orally or intravenously represents the standard of care for malignant gliomas, its efficacy is unsatisfactory. Read More

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Patient specific, imaging-informed modeling of rhenium-186 nanoliposome delivery via convection-enhanced delivery in glioblastoma multiforme.

Biomed Phys Eng Express 2021 May 28;7(4). Epub 2021 May 28.

Biomedical Engineering, The University of Texas at Austin, Austin, Texas, United States of America.

Convection-enhanced delivery of rhenium-186 (Re)-nanoliposomes is a promising approach to provide precise delivery of large localized doses of radiation for patients with recurrent glioblastoma multiforme. Current approaches for treatment planning utilizing convection-enhanced delivery are designed for small molecule drugs and not for larger particles such asRe-nanoliposomes. To enable the treatment planning forRe-nanoliposomes delivery, we have developed a computational fluid dynamics approach to predict the distribution of nanoliposomes for individual patients. Read More

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Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance.

Nat Biomed Eng 2021 May 27. Epub 2021 May 27.

Department of Biomedical Engineering, Yale University, New Haven, CT, USA.

In patients with glioblastoma, resistance to the chemotherapeutic temozolomide (TMZ) limits any survival benefits conferred by the drug. Here we show that the convection-enhanced delivery of nanoparticles containing disulfide bonds (which are cleaved in the reductive environment of the tumour) and encapsulating an oxaliplatin prodrug and a cationic DNA intercalator inhibit the growth of TMZ-resistant cells from patient-derived xenografts, and hinder the progression of TMZ-resistant human glioblastoma tumours in mice without causing any detectable toxicity. Genome-wide RNA profiling and metabolomic analyses of a glioma cell line treated with the cationic intercalator or with TMZ showed substantial differences in the signalling and metabolic pathways altered by each drug. Read More

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Convection-Enhanced Delivery and Principles of Extracellular Transport in the Brain.

World Neurosurg 2021 07 24;151:163-171. Epub 2021 May 24.

Department of Neurological Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.

Stereotactic neurosurgery involves a targeted intervention based on congruence of image guidance to a reference fiducial system. This discipline has widespread applications in radiosurgery, tumor therapy, drug delivery, functional lesioning, and neuromodulation. In this article, we focused on convection-enhanced delivery to deliver therapeutic agents to the brain addressing areas of research and clinical development. Read More

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The emerging role of nanotechnology in pursuit of successful drug delivery to H3K27M diffuse midline gliomas.

Nanomedicine (Lond) 2021 07 17;16(16):1343-1346. Epub 2021 May 17.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

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Evaluation of a patient-specific algorithm for predicting distribution for convection-enhanced drug delivery into the brainstem of patients with diffuse intrinsic pontine glioma.

J Neurosurg Pediatr 2021 May 14:1-9. Epub 2021 May 14.

2Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York.

Objective: With increasing use of convection-enhanced delivery (CED) of drugs, the need for software that can predict infusion distribution has grown. In the context of a phase I clinical trial for pediatric diffuse intrinsic pontine glioma (DIPG), CED was used to administer an anti-B7H3 radiolabeled monoclonal antibody, iodine-124-labeled omburtamab. In this study, the authors retrospectively evaluated a software algorithm (iPlan Flow) for the estimation of infusate distribution based on the planned catheter trajectory, infusion parameters, and patient-specific MRI. Read More

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Convection-enhanced delivery for H3K27M diffuse midline glioma: how can we efficaciously modulate the blood-brain barrier?

Ther Deliv 2021 06 5;12(6):419-422. Epub 2021 May 5.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

Graphical abstract [Formula: see text]. Read More

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Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.

Neuromolecular Med 2021 May 4. Epub 2021 May 4.

Applied Biology Division, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, 500007, Telangana, India.

Based on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X-linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric disorders. Further elucidation of the neuroprotective and neurorestorative properties of VOR using proper clinical study designs could provide momentum towards its clinical application. Read More

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Convection Enhanced Delivery in the Setting of High-Grade Gliomas.

Pharmaceutics 2021 Apr 15;13(4). Epub 2021 Apr 15.

OncoSynergy, Inc., Stamford, CT 06902, USA.

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood-brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas. Read More

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β-Cyclodextrin-poly (β-Amino Ester) Nanoparticles Are a Generalizable Strategy for High Loading and Sustained Release of HDAC Inhibitors.

ACS Appl Mater Interfaces 2021 May 27;13(18):20960-20973. Epub 2021 Apr 27.

Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, Texas 77030, United States.

Therapeutic development of histone deacetylase inhibitors (HDACi) has been hampered by a number of barriers to drug delivery, including poor solubility and inadequate tissue penetration. Nanoparticle encapsulation could be one approach to improve the delivery of HDACi to target tissues; however, effective and generalizable loading of HDACi within nanoparticle systems remains a long-term challenge. We hypothesized that the common terminally ionizable moiety on many HDACi molecules could be capitalized upon for loading in polymeric nanoparticles. Read More

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Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma.

Clin Cancer Res 2021 Jul 16;27(14):3916-3925. Epub 2021 Apr 16.

Medicenna BioPharma, Houston, Texas.

Purpose: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM).

Patients And Methods: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. Read More

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Therapeutic Delivery to Central Nervous System.

Neurosurg Clin N Am 2021 Apr 18;32(2):291-303. Epub 2021 Feb 18.

Department of Neuro-Oncology, Neuro-Oncology Program, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. Electronic address:

Therapies for glioblastoma face several physiologic hurdles. The blood-brain barrier (BBB) and blood-brain-tumor barrier (BTB) present impediments to therapeutic delivery of drugs to the central nervous system. Strategies to disrupt or bypass the native BBB are necessary to deliver therapeutic agents. Read More

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Convection-enhanced drug delivery for glioblastoma: a review.

J Neurooncol 2021 Feb 21;151(3):415-427. Epub 2021 Feb 21.

Department of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, NY, USA.

Introduction: Convection-enhanced delivery (CED) is a method of targeted, local drug delivery to the central nervous system (CNS) that bypasses the blood-brain barrier (BBB) and permits the delivery of high-dose therapeutics to large volumes of interest while limiting associated systemic toxicities. Since its inception, CED has undergone considerable preclinical and clinical study as a safe method for treating glioblastoma (GBM). However, the heterogeneity of both, the surgical procedure and the mechanisms of action of the agents studied-combined with the additional costs of performing a trial evaluating CED-has limited the field's ability to adequately assess the durability of any potential anti-tumor responses. Read More

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February 2021

Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy.

Int J Clin Oncol 2021 Apr 11;26(4):647-658. Epub 2021 Feb 11.

Harley Street Children's Hospital, London, UK.

Purpose: Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). Read More

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Pediatric high-grade glioma: moving toward subtype-specific multimodal therapy.

FEBS J 2021 Feb 1. Epub 2021 Feb 1.

Department of Pediatrics, Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Aurora, CO, USA.

Pediatric high-grade gliomas (pHGG) comprise a deadly, heterogenous category of pediatric gliomas with a clear need for more effective treatment options. Advances in high-throughput molecular techniques have enhanced molecular understanding of these tumors, but outcomes are still poor, and treatments beyond resection and radiation have not yet been clearly established as standard of care. In this review, we first discuss the history of treatment approaches to pHGG to this point. Read More

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February 2021

Intrastriatal Administration of AAV5-miHTT in Non-Human Primates and Rats Is Well Tolerated and Results in miHTT Transgene Expression in Key Areas of Huntington Disease Pathology.

Brain Sci 2021 Jan 20;11(2). Epub 2021 Jan 20.

Madeha Management & Consultancy, 1222 LM Nederhorst den Berg, The Netherlands.

Huntington disease (HD) is a fatal, neurodegenerative genetic disorder with aggregation of mutant Huntingtin protein (mutHTT) in the brain as a key pathological mechanism. There are currently no disease modifying therapies for HD; however, -lowering therapies hold promise. Recombinant adeno-associated virus serotype 5 expressing a microRNA that targets mRNA (AAV5-miHTT) is in development for the treatment of HD with promising results in rodent and minipig HD models. Read More

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January 2021

Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging.

Pharmaceutics 2020 Dec 30;13(1). Epub 2020 Dec 30.

OncoSynergy, Inc., Stamford, CT 06902, USA.

Introduction: OS2966 is a first-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Read More

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December 2020

Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience.

Pharmaceutics 2020 Dec 30;13(1). Epub 2020 Dec 30.

Department of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.

A key limitation to glioma treatment involves the blood brain barrier (BBB). Convection enhanced delivery (CED) is a technique that uses a catheter placed directly into the brain parenchyma to infuse treatments using a pressure gradient. In this manuscript, we describe the physical principles behind CED along with the common pitfalls and methods for optimizing convection. Read More

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December 2020

Phase I trial of intracerebral convection-enhanced delivery of carboplatin for treatment of recurrent high-grade gliomas.

PLoS One 2020 29;15(12):e0244383. Epub 2020 Dec 29.

Department of Neurological Surgery, The Ohio State University College of Medicine Wexner Medical Center, Columbus, Ohio, United States of America.

Background: Carboplatin is a potent cytoreductive agent for a variety of solid tumors. However, when delivered systemically, clinical efficacy for the treatment of high grade gliomas is poor due to limited penetration across the blood-brain barrier (BBB). Direct intracerebral (IC) convection-enhanced delivery (CED) of carboplatin has been used to bypass the BBB and successfully treat the F98 rat glioma. Read More

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Surgical methodology and protocols for preventing implanted cerebral catheters from becoming obstructed during and after neurosurgery.

J Neurosci Methods 2021 02 4;349:109020. Epub 2020 Dec 4.

Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, 40536, United States. Electronic address:

Background: Convection Enhanced Delivery (CED) into targeted brain areas has been tested in animal models and clinical trials for the treatment of various neurological diseases.

New Method: We used a series of techniques, to in effect, maintain positive pressure inside the catheter relative to the outside, that included a hollow stylet, a high volume bolus of solution to clear the line, a low and slow continuous flow rate during implantation, and heat sealing the catheter at the time of implantation.

Results: 120 catheters implanted into brain parenchyma of 89 adult female rhesus monkeys across four sets of experiments. Read More

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February 2021