Implantable Systems for Drug Delivery to the Brain

Kaurav, Hemlata; Kapoor, Deepak

doi:10.4155/tde-2017-0082

Cited by 19 publications

(14 citation statements)

References 77 publications

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“…In this study, we performed multiple intracranial treatments; in the future one may consider the development of slow-release formulations, or continuous low flow infusion to better control the immune response and alleviate the edema and complications associated with immunotherapy. Delivery of therapeutics to the brain is an active area of research that has evolved from biodegradable polymer implants [65,66] to more recent miniaturized implantable system MiNDS [67]. We have already developed and tested slow-release formulations for VLP vaccines [68], including in situ vaccines [69].…”

Section: Discussionmentioning

confidence: 99%

Plant Virus-Like Particle In Situ Vaccine for Intracranial Glioma Immunotherapy

Kerstetter-Fogle

Shukla

Wang

et al. 2019

Cancers

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Despite aggressive multi-modality treatment with surgery, radiation and chemotherapies, malignant glioma inevitably recurs and has dismal survival rates. Recent progress in immunotherapy has led to a resurgence of interest, and immunotherapies are being investigated for treatment of glioma. However, the unique brain anatomy and a highly immunosuppressive glioma microenvironment pose significant challenges to achieving efficacy. Thus, there is a critical need for assessment of next-generation immunotherapies for glioma. In this study, we have investigated the efficacy of the nanoparticle platform technology based on plant-derived Cowpea mosaic virus like particles (empty CPMV or eCPMV) to instigate a potent immune response against intracranial glioma. CPMV immunotherapy has been shown to efficiently reverse the immunosuppressive tumor microenvironments in pre-clinical murine models of dermal melanoma and metastatic melanoma, metastatic breast cancer, intraperitoneal ovarian cancer and in canine patients with oral melanoma. In the present study, we demonstrate that in situ administration of CPMV immunotherapy in the setting of glioma can effectively recruit unique subset of effector innate and adaptive immune cells to the brain parenchyma while reducing immune suppressive cellular population, leading to regression of intracranial glioma. The in situ CPMV nanoparticle vaccine offers a potent yet safe and localized immunotherapy for intracranial glioma.

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Section: Discussionmentioning

confidence: 99%

Plant Virus-Like Particle In Situ Vaccine for Intracranial Glioma Immunotherapy

Kerstetter-Fogle

Shukla

Wang

et al. 2019

Cancers

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“…Implants that do not penetrate the brain are in many cases preferable to brain‐penetrating ones, as the latter cause more tissue damage and increase risk for the patient. To that end, there have been multiple devices designed for drug delivery within the intracranial space between brain and skull including gels and tablets that release drugs as they dissolve and various systems that allow for fluidic injection of drugs . However, fluidic drug injection systems have been plagued by problems with clogging and reflux while the single‐use nature of dissolving implants is not well suited for the treatment of chronic disorders.…”

mentioning

confidence: 99%

An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo

et al. 2018

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The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it is needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (µFIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The µFIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug‐delivery systems.

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“…Polyplexed DNA complexes with PEI generally show an increased stability in human serum (Moret et al, 2001;García et al, 2012) thus supporting the use of this complexed form of DNA for GBM treatment. In this kind of tumor, the BBB is generally damaged, thus allowing for delivery of drugs via systemic injection, however, due to the particular CNS location, it would be possible and may be preferred, to treat the patients via local infusions or even allowing the release of drugs by automated and programmable devices (Kaurav and Kapoor 2017;Yu et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells

et al. 2021

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A novel suicide gene therapy approach was tested in U87 MG glioblastoma multiforme cells. A 26nt G-rich double-stranded DNA aptamer (AS1411) was integrated into a vector at the 5′ of a mammalian codon-optimized saporin gene, under CMV promoter. With this plasmid termed “APTSAP”, the gene encoding ribosome-inactivating protein saporin is driven intracellularly by the glioma-specific aptamer that binds to cell surface-exposed nucleolin and efficiently kills target cells, more effectively as a polyethyleneimine (PEI)-polyplex. Cells that do not expose nucleolin at the cell surface such as 3T3 cells, used as a control, remain unaffected. Suicide gene-induced cell killing was not observed when the inactive saporin mutant SAPKQ DNA was used in the (PEI)-polyplex, indicating that saporin catalytic activity mediates the cytotoxic effect. Rather than apoptosis, cell death has features resembling autophagic or methuosis-like mechanisms. These main findings support the proof-of-concept of using PEI-polyplexed APTSAP for local delivery in rat glioblastoma models.

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Implantable Systems for Drug Delivery to the Brain

Cited by 19 publications

References 77 publications

Plant Virus-Like Particle In Situ Vaccine for Intracranial Glioma Immunotherapy

Plant Virus-Like Particle In Situ Vaccine for Intracranial Glioma Immunotherapy

An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo

Aptamer-Driven Toxin Gene Delivery in U87 Model Glioblastoma Cells

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