467 results match your criteria delivery ced

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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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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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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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 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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Visceral pressure stimulator for exploring hollow organ pain: a pilot study.

Biomed Eng Online 2021 Mar 25;20(1):30. Epub 2021 Mar 25.

Center for Advanced Pain Studies, Department of Neuroscience, University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.

Background: The regulation and control of pressure stimuli is useful for many studies of pain and nociception especially those in the visceral pain field. In many in vivo experiments, distinct air and liquid stimuli at varying pressures are delivered to hollow organs such as the bladder, vagina, and colon. These stimuli are coupled with behavioral, molecular, or physiological read-outs of the response to the stimulus. 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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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

Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor.

Pharmaceutics 2020 Dec 24;13(1). Epub 2020 Dec 24.

Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.

The presence of blood-brain barrier (BBB) and/or blood-brain-tumor barriers (BBTB) is one of the main obstacles to effectively deliver therapeutics to our central nervous system (CNS); hence, the outcomes following treatment of malignant brain tumors remain unsatisfactory. Although some approaches regarding BBB disruption or drug modifications have been explored, none of them reach the criteria of success. Convention-enhanced delivery (CED) directly infuses drugs to the brain tumor and surrounding tumor infiltrating area over a long period of time using special catheters. 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

Use of a novel ball-joint guide array for magnetic resonance imaging-guided cannula placement and convective delivery: technical note.

J Neurosurg 2020 Oct 23:1-7. Epub 2020 Oct 23.

2Department of Neurological Surgery, Centrum Medyczne Kształcenia Podyplomowego, Brodno Hospital, Warsaw, Poland.

Objective: The objective of this study was to assess the feasibility, accuracy, effectiveness, and safety of an MRI-compatible frameless stereotactic ball-joint guide array (BJGA) as a platform for cannula placement and convection-enhanced delivery (CED).

Methods: The authors analyzed the clinical and imaging data from consecutive patients with aromatic l-amino acid decarboxylase (AADC) deficiency who underwent infusion of adeno-associated virus (AAV) containing the AADC gene (AAV2-AADC).

Results: Eleven patients (7 females, 4 males) underwent bilateral MRI-guided BJGA cannula placement and CED of AAV2-AADC (22 brainstem infusions). Read More

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October 2020

Current strategies for the treatment of malignant gliomas - experience of the Department of Neurosurgery, Brodno Masovian Hospital in Warsaw.

Pol Przegl Chir 2020 Jun;92(5):1-5

Department of Neurosurgery, Brodno Masovian Hospital, Warsaw, Poland, Gamma Knife Centre, Warsaw, Poland, Department of Neurosurgery, Postgraduate Medical Centre, Warsaw, Poland, Interventional Neuro Center, Brodno Masovian Hospital, Warsaw, Poland.

Introduction: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. Read More

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Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma.

J Neurosurg Pediatr 2020 Sep 25:1-6. Epub 2020 Sep 25.

1Department of Neurological Surgery, NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York.

Objective: While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single-dose drug infusions, agents for oncological therapy may require repeated or chronic infusions to maintain therapeutic drug concentrations. Repeat and chronic CED infusions have rarely been described for oncological purposes. Currently available CED devices are not approved for extended indwelling use, and the only potential at this time is for sequential treatments through multiple procedures. Read More

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September 2020

Determinants of Intraparenchymal Infusion Distributions: Modeling and Analyses of Human Glioblastoma Trials.

Pharmaceutics 2020 Sep 21;12(9). Epub 2020 Sep 21.

Department of Neurosurgery, Duke University, Durham, NC 27710, USA.

Intra-parenchymal injection and delivery of therapeutic agents have been used in clinical trials for brain cancer and other neurodegenerative diseases. The complexity of transport pathways in tissue makes it difficult to envision therapeutic agent distribution from clinical MR images. Computer-assisted planning has been proposed to mitigate risk for inadequate delivery through quantitative understanding of infusion characteristics. Read More

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September 2020

Infusion Mechanisms in Brain White Matter and Their Dependence on Microstructure: An Experimental Study of Hydraulic Permeability.

IEEE Trans Biomed Eng 2021 04 18;68(4):1229-1237. Epub 2021 Mar 18.

Objective: Hydraulic permeability is a topic of deep interest in biological materials because of its important role in a range of drug delivery-based therapies. The strong dependence of permeability on the geometry and topology of pore structure and the lack of detailed knowledge of these parameters in the case of brain tissue makes the study more challenging. Although theoretical models have been developed for hydraulic permeability, there is limited consensus on the validity of existing experimental evidence to complement these models. Read More

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Direct convective delivery of adeno-associated virus gene therapy for treatment of neurological disorders.

J Neurosurg 2020 Jul 10:1-13. Epub 2020 Jul 10.

1Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio; and.

Molecular biological insights have led to a fundamental understanding of the underlying genomic mechanisms of nervous system disease. These findings have resulted in the identification of therapeutic genes that can be packaged in viral capsids for the treatment of a variety of neurological conditions, including neurodegenerative, metabolic, and enzyme deficiency disorders. Recent data have demonstrated that gene-carrying viral vectors (most often adeno-associated viruses) can be effectively distributed by convection-enhanced delivery (CED) in a safe, reliable, targeted, and homogeneous manner across the blood-brain barrier. Read More

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Integrating Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging to Improve the Predictive Capabilities of CED Models.

Ann Biomed Eng 2021 Feb 3;49(2):689-702. Epub 2020 Sep 3.

Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.

This paper aims to develop a comprehensive and subject-specific model to predict the drug reach in Convection-Enhanced Delivery (CED) interventions. To this end, we make use of an advance diffusion imaging technique, namely the Neurite Orientation Dispersion and Density Imaging (NODDI), to incorporate a more precise description of the brain microstructure into predictive computational models. The NODDI dataset is used to obtain a voxel-based quantification of the extracellular space volume fraction that we relate to the white matter (WM) permeability. Read More

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February 2021

PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models.

Sci Adv 2020 Jul 24;6(30):eabb4105. Epub 2020 Jul 24.

Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.

Efforts at altering the dismal prognosis of pediatric midline gliomas focus on direct delivery strategies like convection-enhanced delivery (CED), where a cannula is implanted into tumor. Successful CED treatments require confirmation of tumor coverage, dosimetry, and longitudinal in vivo pharmacokinetic monitoring. These properties would be best determined clinically with image-guided dosimetry using theranostic agents. Read More

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Phase I trial of convection-enhanced delivery of IL13RA2 and EPHA2 receptor targeted cytotoxins in dogs with spontaneous intracranial gliomas.

Neuro Oncol 2021 03;23(3):422-434

Comprehensive Cancer Center and Brain Tumor Center of Excellence of Wake Forest University, Winston-Salem, North Carolina.

Background: The interleukin-13 receptor alpha 2 (IL13RA2) and ephrin type A receptor 2 (EPHA2) are attractive therapeutic targets, being expressed in ~90% of canine and human gliomas, and absent in normal brain. Clinical trials using an earlier generation IL-13 based cytotoxin showed encouraging clinical effects in human glioma, but met with technical barriers associated with the convection-enhanced delivery (CED) method. In this study, IL-13 mutant and ephrin A1 (EFNA1)-based bacterial cytotoxins targeted to IL13RA2 and EPHA2 receptors, respectively, were administered locoregionally by CED to dogs with intracranial gliomas to evaluate their safety and preliminary efficacy. Read More

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Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma.

J Neurooncol 2020 Sep 18;149(2):193-208. Epub 2020 Aug 18.

Department of Pathology, The Ohio State University, 4132 Graves Hall - 333 W. 10th Avenue, Columbus, OH, 43210, USA.

Background: The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c. Read More

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September 2020

Controlled Catheter Movement Affects Dye Dispersal Volume in Agarose Gel Brain Phantoms.

Pharmaceutics 2020 Aug 11;12(8). Epub 2020 Aug 11.

Walker Department of Mechanical Engineering, The University of Texas at Austin, 204 E. Dean Keeton Street, Stop C2200, Austin, TX 78712-1591, USA.

The standard of care for treatment of glioblastoma results in a mean survival of only 12 to 15 months. Convection-enhanced delivery (CED) is an investigational therapy to treat glioblastoma that utilizes locoregional drug delivery via a small-caliber catheter placed into the brain parenchyma. Clinical trials have failed to reach their endpoints due to an inability of standard catheters to fully saturate the entire brain tumor and its margins. Read More

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Inflammatory Mediators in Glioma Microenvironment Play a Dual Role in Gliomagenesis and Mesenchymal Stem Cell Homing: Implication for Cellular Therapy.

Mayo Clin Proc Innov Qual Outcomes 2020 Aug 5;4(4):443-459. Epub 2020 Aug 5.

Department of Neurosurgery, Mayo Clinic, Jacksonville, FL.

Glioblastoma is the most aggressive malignant primary brain tumor, with a dismal prognosis and a devastating overall survival. Despite aggressive surgical resection and adjuvant treatment, average survival remains approximately 14.6 months. Read More

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Convection Enhanced Delivery for Diffuse Intrinsic Pontine Glioma: Review of a Single Institution Experience.

Pharmaceutics 2020 Jul 14;12(7). Epub 2020 Jul 14.

Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.

Diffuse intrinsic pontine gliomas (DIPGs) are a pontine subtype of diffuse midline gliomas (DMGs), primary central nervous system (CNS) tumors of childhood that carry a terrible prognosis. Because of the highly infiltrative growth pattern and the anatomical position, cytoreductive surgery is not an option. An initial response to radiation therapy is invariably followed by recurrence; mortality occurs approximately 11 months after diagnosis. Read More

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Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma.

Neurosurgery 2020 Jul 16. Epub 2020 Jul 16.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background: Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brain tumor and the majority of patients die within 2 yr after initial diagnosis. Factors that contribute to the dismal prognosis of these patients include the infiltrative nature and anatomic location in an eloquent area of the brain, which precludes total surgical resection, and the presence of the blood-brain barrier (BBB), which reduces the distribution of systemically administered agents. Convection-enhanced delivery (CED) is a direct infusion technique to deliver therapeutic agents into a target site in the brain and able to deliver a high concentration drug to the infusion site without systemic toxicities. Read More

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