Convection enhanced delivery

Adeno-associated virus (AAV) has been demonstrated to be a clinically useful gene delivery vehicle for treating neurological diseases. To deliver AAV to focal targets, direct infusion into brain tissue by convection-enhanced delivery (CED) is often needed due to AAV's limited penetration across the blood-brain-barrier and its low tissue diffusivity. In this study, computational models that predict the spatial distribution of AAV in brain tissue during CED were developed to guide surgical placement of infusion catheters in recurrent brain tumors following primary tumor resection...

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy...

The use of antibody-conjugated nanoparticles for brain tumor treatment has gained significant attention in recent years. Nanoparticles functionalized with anti-transferrin receptor antibodies have shown promising results in facilitating nanoparticle uptake by endothelial cells of brain capillaries and post-capillary venules. This approach offers a potential alternative to the direct conjugation of biologics to antibodies. Furthermore, studies have demonstrated the potential of antibody-conjugated nanoparticles in targeting brain tumors, as evidenced by the specific binding of these nanoparticles to brain cancer cells...

Convection-enhanced drug delivery (CED) directly infuses drugs with a large molecular weight toward target cells as a therapeutic strategy for neurodegenerative diseases and brain cancers. Despite the success of many previous in vitro experiments on CED, challenges still remain. In particular, a theoretical predictive model is needed to form a basis for treatment planning, and developing such a model requires well-controlled injection tests that can rigorously capture the convective (advective) and diffusive transport of an infusate...

The evaluation of the efficacy of a drug is a fundamental step in the development of new treatments or in personalized therapeutic strategies and patient management. Ideally, this evaluation should be rapid, possibly in real time, easy to perform and reliable. In addition, it should be associated with as few adverse effects as possible for the patient. In this study, we present a device designed to meet these goals for assessing therapeutic response. This theranostic device is based on the use of magnetic resonance imaging and spectroscopy for the diagnostic aspect and on the application of the convection-enhanced delivery technique for the therapeutic aspect...

Glioblastoma, a grade 4 glioma as per the World Health Organization, poses a challenge in adult primary brain tumor management despite advanced surgical techniques and multimodal therapies. This review delves into the potential of targeting epidermal growth factor receptor (EGFR) with small-molecule inhibitors and antibodies as a treatment strategy. EGFR, a mutationally active receptor tyrosine kinase in over 50% of glioblastoma cases, features variants like EGFRvIII, EGFRvII and missense mutations, necessitating a deep understanding of their structures and signaling pathways...

OBJECTIVE: Breast cancer is a global health concern that demands attention. In our contribution to addressing this disease, our study focuses on investigating a wireless micro-device for intratumoral drug delivery, utilizing electrochemical actuation. Microdevices have emerged as a promising approach in this field due to their ability to enable controlled injections in various applications. METHODS: Our study is conducted within a computational framework, employing models that simulate the behavior of the microdevice and drug discharge based on the principles of the ideal gas law...

Micro/nanorobotic swarms consisting of numerous tiny building blocks show great potential in biomedical applications because of their collective active delivery ability, enhanced imaging contrast, and environment-adaptive capability. However, in vivo real-time imaging and tracking of micro/nanorobotic swarms remain a challenge, considering the limited imaging size and spatial-temporal resolution of current imaging modalities. Here, we propose a strategy that enables real-time tracking and navigation of a microswarm in stagnant and flowing blood environments by using laser speckle contrast imaging (LSCI), featuring full-field imaging, high temporal-spatial resolution, and noninvasiveness...

PURPOSE OF REVIEW: To review relevant advances in the past half-decade in the treatment of primary brain tumors via modification of blood-brain barrier (BBB) permeability. RECENT FINDINGS: BBB disruption is becoming increasingly common in the treatment of primary brain tumors. Use of mannitol in BBB disruption for targeted delivery of chemotherapeutics via superselective intra-arterial cerebral infusion (SIACI) is the most utilized strategy to modify the BBB. Mannitol is used in conjunction with chemotherapeutics, oligonucleotides, and other active agents...

Although the brain is very accessible to nutrition and oxygen, it can be difficult to deliver medications to malignant brain tumours. To get around some of these issues and enable the use of therapeutic pharmacological substances that wouldn't typically cross the blood-brain barrier (BBB), convection-enhanced delivery (CED) has been developed. It is a cutting-edge strategy that gets beyond the blood-brain barrier and enables targeted drug administration to treat different neurological conditions such as brain tumours, Parkinson's disease, and epilepsy...

BACKGROUND: Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been developed in vitro, these putative therapeutics have not been translated into successful clinical treatments. The lack of clinical effectiveness can be the result of ineffective biologic strategies, heterogeneous tumor targets and/or the result of poortherapeutic distribution to malignant glioma cells using conventional nervous system delivery modalities (intravascular, cerebrospinal fluid and/orpolymer implantation), and/or ineffective biologic strategies...

This groundbreaking study pioneers the exploration of the therapeutic implications of a constant magnetic field simultaneously with hybrid nanoparticles on blood flow within a tapered artery, characterized by multiple stenosis along its exterior walls and a central thrombus, employing three-dimensional bio-fluid simulations. In addition, a magnetized catheter is inserted into the thrombus to increase the therapeutic potential of this novel method. The flow condition under consideration has applications in targeted medication distribution, improved medical device design, and improved diagnostics, as well as in advancing healthcare and biomedical engineering...

BACKGROUND AND OBJECTIVE: 177 Lu-labeled prostate-specific membrane antigen (PSMA) radiopharmaceutical therapy (RPT) represents a pivotal advancement in addressing prostate cancer. However, existing therapies, while promising, remain incompletely understood and optimized. Computational models offer potential insights into RPTs, aiding in clinical drug delivery enhancement. In this study, we investigate the impact of various physiological parameters on the delivery of 177 Lu-PSMA-617 RPT using the convection-diffusion-reaction (CDR) model...

OBJECTIVE: Relatively little is known about the safety and accuracy of catheter placement for oncolytic viral therapy in children with malignant brain tumors. Accordingly, this study combines data from two phase I clinical trials that employed viral immunotherapy across two institutions to describe the adverse event profile, safety, and accuracy associated with the stereotactic placement and subsequent removal of intratumoral catheters. METHODS: Children with progressive/recurrent supratentorial malignant tumors were enrolled in two clinical trials (NCT03043391 and NCT02457845) and treated with either the recombinant polio:rhinovirus (lerapolturev) or the genetically modified oncolytic herpesvirus (G207)...

The blood-brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant brain tissue and only restricted access to primary and metastatic brain cancers. Consequently, due to the drug's inability to effectively penetrate the BBB, outcomes following brain chemotherapy continue to be suboptimal. Several methods to open the BBB and obtain higher drug concentrations in tumors have been proposed, with the selection of the optimal method depending on the size of the targeted tumor volume, the chosen therapeutic agent, and individual patient characteristics...

Drug delivery systems which rely on diffusion for mass transport, such as hydrogels and nanoparticles, have enhanced drug targeting and extended delivery profiles to improve health outcomes for patients suffering from diseases including cancer and diabetes. However, diffusion-dependent systems often fail to provide >0.01-1% drug bioavailability when transporting macromolecules across poorly permeable physiological tissues such as the skin, solid tumors, the blood-brain barrier, and the gastrointestinal walls...

Targeted intracerebral drug delivery is an attractive experimental approach for the treatment of drug-resistant epilepsies. In this regard, the subthalamic nucleus (STN) represents a focus-independent target involved in the remote modulation and propagation of seizure activity. Indeed, acute and chronic pharmacological inhibition of the STN with vigabatrin (VGB), an irreversible inhibitor of GABA transaminase, has been shown to produce antiseizure effects. This effect, however, is lost over time as tolerance develops with chronic, continuous intracerebral pharmacotherapy...

Neurological disorders are a significant societal and economic burden. Common pharmacological therapies often can only manage symptoms and have limited efficacy. Intraparenchymal convection enhanced delivery (IP CED) is a neurosurgical technique for direct brain delivery of therapeutics. Currently, the main applications of IP CED are targeted chemotherapy for glioblastoma and gene therapy. While IP CED has advantages over systemic approaches, its benefits can be drastically reduced by inadequate coverage as low as 21% of target anatomy, excessive infusion durations greater than 2 hours, and off-target effects...

Adenoviruses are well-known viral vectors that have been previously used in gene therapy and as a vaccine-delivery vehicle for humans and animals. During the COVID-19 pandemic, it gained renewed attention, but at the same time, it raised concerns due to side effects observed with some of the resulting vaccines administered to patients. It has been indicated that these side effects might be attributed to impurities present in the final product. Therefore, constant enhancement of the vaccine purity and further improvement of impurity detection methods are needed...

Glioblastoma is characterized by diffuse infiltration into surrounding healthy brain tissues, which makes it challenging to treat. Complete surgical resection is often impossible, and systemically delivered drugs cannot achieve adequate tumor exposure to prevent local recurrence. Convection-enhanced delivery (CED) offers a method for administering therapeutics directly into brain tumor tissue, but its impact has been limited by rapid clearance and off-target cellular uptake. Nanoparticle (NP) encapsulation presents a promising strategy for extending the retention time of locally delivered therapies while specifically targeting glioblastoma cells...