Improving the Efficacy and Accessibility of Intracranial Viral Vector Delivery in Non-Human Primates

Griggs, Devon J.; Garcia, Aaron D.; Au, Wing Yun; Ojemann, William K. S.; Johnson, Andrew Graham; Ting, Jonathan T.; Buffalo, Elizabeth A.; Yazdan-Shahmorad, Azadeh

doi:10.3390/pharmaceutics14071435

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Several authors have used MRI agarose phantoms to characterise diffusion (16,(19)(20)(21). Wyatt et al developed a physical brain phantom for MRI, mimicking structure and T 1 relaxation properties of white matter and grey matter.…”

Section: Radial Distance From the Point Of Infusionmentioning

confidence: 99%

In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study

Zimphango,

Mada,

Sawiak

et al. 2024

Front. Radiol.

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Rationale and objectivesCerebral microdialysis is a technique that enables monitoring of the neurochemistry of patients with significant acquired brain injury, such as traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Cerebral microdialysis can also be used to characterise the neuro-pharmacokinetics of small-molecule study substrates using retrodialysis/retromicrodialysis. However, challenges remain: (i) lack of a simple, stable, and inexpensive brain tissue model for the study of drug neuropharmacology; and (ii) it is unclear how far small study-molecules administered via retrodialysis diffuse within the human brain.Materials and methodsHere, we studied the radial diffusion distance of small-molecule gadolinium-DTPA from microdialysis catheters in a newly developed, simple, stable, inexpensive brain tissue model as a precursor for in-vivo studies. Brain tissue models consisting of 0.65% weight/volume agarose gel in two kinds of buffers were created. The distribution of a paramagnetic contrast agent gadolinium-DTPA (Gd-DTPA) perfusion from microdialysis catheters using magnetic resonance imaging (MRI) was characterized as a surrogate for other small-molecule study substrates.ResultsWe found the mean radial diffusion distance of Gd-DTPA to be 18.5 mm after 24 h (p < 0.0001).ConclusionOur brain tissue model provides avenues for further tests and research into infusion studies using cerebral microdialysis, and consequently effective focal drug delivery for patients with TBI and other brain disorders.

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Section: Radial Distance From the Point Of Infusionmentioning

confidence: 99%

In-vitro gadolinium retro-microdialysis in agarose gel—a human brain phantom study

Zimphango,

Mada,

Sawiak

et al. 2024

Front. Radiol.

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“…To overcome these challenges, several administration routes have been explored including intranasal and intracranial routes. [20][21][22] Focusing on intravenous administration, nanosized carriers (nanoparticles (NPs), size >100 nm) 23 are increasingly being developed for more efficient drug delivery across the BBB for the treatment and diagnosis of a wide range of CNS diseases, such as cancer and neurodegenerative diseases. 5,[24][25][26] In addition, different precision targeting strategies (eg, functionalization with antibodies, ligand proteins or homing peptides) have been explored to facilitate drug uptake into the brain.…”

Section: Introductionmentioning

confidence: 99%

Brain Targeting Nanomedicines: Pitfalls and Promise

Kakinen,

Jiang,

Davis

et al. 2024

IJN

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Brain diseases are the most devastating problem among the world's increasingly aging population, and the number of patients with neurological diseases is expected to increase in the future. Although methods for delivering drugs to the brain have advanced significantly, none of these approaches provide satisfactory results for the treatment of brain diseases. This remains a challenge due to the unique anatomy and physiology of the brain, including tight regulation and limited access of substances across the blood-brain barrier. Nanoparticles are considered an ideal drug delivery system to hard-to-reach organs such as the brain. The development of new drugs and new nanomaterial-based brain treatments has opened various opportunities for scientists to develop brain-specific delivery systems that could improve treatment outcomes for patients with brain disorders such as Alzheimer's disease, Parkinson's disease, stroke and brain tumors. In this review, we discuss noteworthy literature that examines recent developments in brain-targeted nanomedicines used in the treatment of neurological diseases.

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“…To improve intracranial viral vector delivery in non-human primates (NHPs), Griggs et al developed a new method based in bench-side convection-enhanced delivery (CED) that provides users with a hands-on CED experience. This method aims to help and guide researchers in the surgical preparations for intracranial viral delivery using CED in NHPs [5]. Indeed, other authors have used CED for the intratumoral administration of biologics.…”

mentioning

confidence: 99%