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Convection-enhanced delivery

Mayur M Patel, Bhoomika M Patel
CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting...
January 18, 2017: CNS Drugs
Vidyalakshmi Chandramohan, Charles N Pegram, Hailan Piao, Scott E Szafranski, Chien-Tsun Kuan, Ira H Pastan, Darell D Bigner
D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initial pre-clinical testing demonstrated the anti-tumor efficacy of D2C7-IT against orthotopic glioblastoma xenograft models expressing EGFRwt, EGFRvIII, or both EGFRwt and EGFRvIII. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a phase I/II clinical trial...
December 24, 2016: Applied Microbiology and Biotechnology
Ryuta Saito, Teiji Tominaga
Convection-enhanced delivery (CED) circumvents the blood-brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED...
December 15, 2016: Neurologia Medico-chirurgica
Helge Thisgaard, Bo Halle, Charlotte Aaberg-Jessen, Birgitte Brinkmann Olsen, Anne Sofie Nautrup Therkelsen, Johan Hygum Dam, Niels Langkjær, Sune Munthe, Kjell Någren, Poul Flemming Høilund-Carlsen, Bjarne Winther Kristensen
Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [(125)I]5-Iodo-2'-deoxyuridine ((125)I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED)...
2016: Theranostics
Madjid Soltani, Mostafa Sefidgar, Hossein Bazmara, Michael E Casey, Rathan M Subramaniam, Richard L Wahl, Arman Rahmim
OBJECTIVE: Distribution of PET tracer uptake is elaborately modeled via a general equation used for solute transport modeling. This model can be used to incorporate various transport parameters of a solid tumor such as hydraulic conductivity of the microvessel wall, transvascular permeability as well as interstitial space parameters. This is especially significant because tracer delivery and drug delivery to solid tumors are determined by similar underlying tumor transport phenomena, and quantifying the former can enable enhanced prediction of the latter...
December 5, 2016: Annals of Nuclear Medicine
Jarushka Naidoo, Hardik Panday, Sadhana Jackson, Stuart A Grossman
Despite significant advances in the treatment of systemic cancers, progress in the treatment of primary brain tumors has been quite modest. In addition, an increasing proportion of patients with systemic cancers are presenting with brain-only metastases. These observations highlight the critical role that the blood-brain barrier plays in preventing antineoplastic therapies from reaching the central nervous system in therapeutic concentrations. This review describes the anatomy of the blood-brain barrier and currently available methods to quantify the entry of therapeutic compounds into the brain...
November 15, 2016: Oncology (Williston Park, NY)
Gwenael Layec, Joel D Trinity, Corey R Hart, Yann Le Fur, Jacob R Sorensen, Eun-Kee Jeong, Russell S Richardson
The purpose of the present study was to determine whether mitochondrial function is limited by O2 availability or the intrinsic capacity of mitochondria to synthesize ATP in elderly individuals. To this aim, we examined, in comparison to free-flow conditions (FF), the effect of superimposing reactive hyperemia (RH), induced by a period of brief ischemia during the last min of exercise, on O2 availability and mitochondrial function in the calf muscle. 12 healthy, untrained, elderly subjects performed dynamic plantar flexion exercise and phosphorus magnetic resonance spectroscopy ((31)P-MRS), near-infrared spectroscopy (NIRS), and Doppler ultrasound were used to assess muscle metabolism and peripheral hemodynamics...
November 6, 2016: Aging
C D Corso, A R King, W M Saltzman, R S Bindra
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
David S Hersh, Anthony J Kim, Jeffrey A Winkles, Howard M Eisenberg, Graeme F Woodworth, Victor Frenkel
: : Transcranial focused ultrasound (FUS) can noninvasively transmit acoustic energy with a high degree of accuracy and safety to targets and regions within the brain. Technological advances, including phased-array transducers and real-time temperature monitoring with magnetic resonance thermometry, have created new opportunities for FUS research and clinical translation. Neuro-oncology, in particular, has become a major area of interest because FUS offers a multifaceted approach to the treatment of brain tumors...
November 2016: Neurosurgery
Dae Gon Lim, Joo Hyun Jung, Hyuk Wan Ko, Eunah Kang, Seong Hoon Jeong
Nanodiamonds (NDs) with 5 nm crystalline structures have been recognized as emerging carbon delivery vehicles due to their biocompatible inertness, high surface-to-volume ratio, and energy absorbance properties. In this study, carboxylated nanodiamond (ND-COOH) was reduced to hydroxylated nanodiamond (ND-OH) for stable and pH-independent colloidal dispersity. The poorly water-soluble paclitaxel (PTX) was physically loaded into ND-OH clusters, forming amorphous PTX nanostructure on the interparticle nanocage of the ND substrate...
September 14, 2016: ACS Applied Materials & Interfaces
Ji Wang, Chengchu Zhu
Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels...
2016: OncoTargets and Therapy
Alice Gaudin, Eric Song, Amanda R King, Jennifer K Saucier-Sawyer, Ranjit Bindra, Didier Desmaële, Patrick Couvreur, W Mark Saltzman
New treatments for glioblastoma multiforme (GBM) are desperately needed, as GBM prognosis remains poor, mainly due to treatment resistance, poor distribution of therapeutics in the tumor tissue, and fast metabolism of chemotherapeutic drugs in the brain extracellular space. Convection-enhanced delivery (CED) of nanoparticles (NPs) has been shown to improve the delivery of chemotherapeutic drugs to the tumor bed, providing sustained release, and enhancing survival of animals with intracranial tumors. Here we administered gemcitabine, a nucleoside analog used as a first line treatment for a wide variety of extracranial solid tumors, within squalene-based NPs using CED, to overcome the above-mentioned challenges of GBM treatment...
October 2016: Biomaterials
Guido Frosina
If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor barriers and reach adequate concentrations at the tumor sites. Effective delivery of drugs to brain cancer tissues is thus a necessary, albeit not sufficient, condition to effectively target the disease. In order to analyze the current status of research on drug delivery to high grade gliomas (HGG-WHO grades III and IV), the most frequent and aggressive brain cancers, a literature search was conducted in PubMed using the terms: "drug delivery and brain tumor" over the publication year 2015...
August 2, 2016: Brain Pathology
Jie Song, Na Li, Yang Xia, Zhong Gao, Sa-Feng Zou, Liang Kong, Ying-Jia Yao, Ya-Nan Jiao, Yu-Hui Yan, Shao-Heng Li, Zhen-Yu Tao, Guan Lian, Jing-Xian Yang, Ting-Guo Kang
UNLABELLED: Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED...
2016: Frontiers in Pharmacology
Paul A Clark, Saswati Bhattacharya, Ardem Elmayan, Soesiawati R Darjatmoko, Bradley A Thuro, Michael B Yan, Paul R van Ginkel, Arthur S Polans, John S Kuo
OBJECTIVE Glioblastoma multiforme (GBM) is an aggressive brain cancer with median survival of less than 2 years with current treatment. Glioblastomas exhibit extensive intratumoral and interpatient heterogeneity, suggesting that successful therapies should produce broad anticancer activities. Therefore, the natural nontoxic pleiotropic agent, resveratrol, was studied for antitumorigenic effects against GBM. METHODS Resveratrol's effects on cell proliferation, sphere-forming ability, and invasion were tested using multiple patient-derived GBM stem-like cell (GSC) lines and established U87 glioma cells, and changes in oncogenic AKT and tumor suppressive p53 were analyzed...
July 15, 2016: Journal of Neurosurgery
Ranjodh Singh, Zhiping Zhou, Jamie Tisnado, Sofia Haque, Kyung K Peck, Robert J Young, Apostolos John Tsiouris, Sunitha B Thakur, Mark M Souweidane
OBJECTIVE Accurately determining diffuse intrinsic pontine glioma (DIPG) tumor volume is clinically important. The aims of the current study were to 1) measure DIPG volumes using methods that require different degrees of subjective judgment; and 2) evaluate interobserver agreement of measurements made using these methods. METHODS Eight patients from a Phase I clinical trial testing convection-enhanced delivery (CED) of a therapeutic antibody were included in the study. Pre-CED, post-radiation therapy axial T2-weighted images were analyzed using 2 methods requiring high degrees of subjective judgment (picture archiving and communication system [PACS] polygon and Volume Viewer auto-contour methods) and 1 method requiring a low degree of subjective judgment (k-means clustering segmentation) to determine tumor volumes...
November 2016: Journal of Neurosurgery. Pediatrics
Xu Wang, Alexa Bodman, Changying Shi, Dandan Guo, Lili Wang, Juntao Luo, Walter A Hall
A strategy to precisely engineer lipidoid-telodendrimer binary hybrid nanoparticles that offer enhanced cell membrane permeability for therapeutic proteins to reach the intracellular targets is established. The highly controllable biochemical and physical properties of the nanoparticles make them promising for protein-based brain cancer treatment with the assistance of convection-enhanced delivery.
August 2016: Small
Rolf F Barth, Gong Wu, W Hans Meisen, Robin J Nakkula, Weilian Yang, Tianyao Huo, David A Kellough, Pravin Kaumaya, Claudia Turro, Lawrence M Agius, Balveen Kaur
The aim of this study was to evaluate four different platinated bioconjugates containing a cisplatin (cis-diamminedichloroplatinum [cis-DDP]) fragment and epidermal growth factor receptor (EGFR)-targeting moieties as potential therapeutic agents for the treatment of brain tumors using a human EGFR-expressing transfectant of the F98 rat glioma (F98EGFR) to assess their efficacy. The first two bioconjugates employed the monoclonal antibody cetuximab (C225 or Erbitux(®)) as the targeting moiety, and the second two used genetically engineered EGF peptides...
2016: OncoTargets and Therapy
Yaxiaer Yalikun, Yoichiroh Hosokawa, Takanori Iino, Yo Tanaka
This study investigated and established a method, using femtosecond laser processing, to fabricate a 100%-glass-based 12 μm ultra-thin and flexible micro-fluidic chip. First we investigated the suitable pulse energy of the laser to fabricate ultra-thin glass sheets and then we fabricated a prototype glass micro-fluidic chip. Two 1 mm-in-diameter orifices for facilitating alignment in the bonding step and one channel with a width of 20 μm and a length of 25 mm were fabricated in a 4 μm thickness ultra-thin glass sheet using the femtosecond laser; this forms layer 2 in the completed device...
July 7, 2016: Lab on a Chip
Moom Sinn Aw, Larysa Paniwnyk, Dusan Losic
INTRODUCTION: Drug delivery pertaining to acoustic cavitation generated from ultrasonic (US) irradiation is advantageous for devising smarter and more advanced therapeutics. The aim is to showcase microbubbles as drug carriers and robust theranostic for non-invasive therapies across diverse biomedical disciplines, highlighting recent technologies in this field for overcoming the blood-brain barrier (BBB) to treat cancers and neurological disorders. AREAS COVERED: This article reviews work on the optimized tuning of ultrasonic parameters, sonoporation, transdermal and responsive drug delivery, acoustic cavitation in vasculature and oncology, contrast imaging for real-time magnification of cell-microbubble dynamics and biomolecular targeting...
October 2016: Expert Opinion on Drug Delivery
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