Governing transport principles for nanotherapeutic application in the brain

Helmbrecht, Hawley; Joseph, Andrea; McKenna, Michael J.; Zhang, Mingjie; Nance, Elizabeth

doi:10.1016/j.coche.2020.08.010

Cited by 8 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No matter if a drug or substance reaches the brain after intranasal delivery, crossing the BBB or direct infusion into the brain, the distribution within the microenvironment involves extracellular diffusion [ 148 ]. Brain distribution can be facilitated by nanotechnology [ 150 ]. Studies have shown that nanotherapeutics and nanomaterials improve the biodistribution of drugs in the brain for more efficient treatment of glioblastoma, not only via convection-enhanced delivery [ 151 ] but also via intranasal delivery [ 152 ].…”

Section: Current Status Of Approved Drugs For Nasal Applicationmentioning

confidence: 99%

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Keller

Merkel

Popp

2021

Drug Deliv. and Transl. Res.

229

178

View full text Add to dashboard Cite

Over the past 10 years, the interest in intranasal drug delivery in pharmaceutical R&D has increased. This review article summarises information on intranasal administration for local and systemic delivery, as well as for CNS indications. Nasal delivery offers many advantages over standard systemic delivery systems, such as its non-invasive character, a fast onset of action and in many cases reduced side effects due to a more targeted delivery. There are still formulation limitations and toxicological aspects to be optimised. Intranasal drug delivery in the field of drug development is an interesting delivery route for the treatment of neurological disorders. Systemic approaches often fail to efficiently supply the CNS with drugs. This review paper describes the anatomical, histological and physiological basis and summarises currently approved drugs for administration via intranasal delivery. Further, the review focuses on toxicological considerations of intranasally applied compounds and discusses formulation aspects that need to be considered for drug development. Graphical abstract

show abstract

Section: Current Status Of Approved Drugs For Nasal Applicationmentioning

confidence: 99%

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Keller

Merkel

Popp

2021

Drug Deliv. and Transl. Res.

229

178

View full text Add to dashboard Cite

show abstract

“…Being able to constrain nanoformulations based on size, ZP, and PDI is an important feature for experiments in probing and treating neurological diseases. Nanoparticle size and surface charge can influence nanoparticle passage across the blood–brain barrier and penetration within the brain parenchyma 5 . In comparison, PDI is an indicator of particle size uniformity.…”

Section: Resultsmentioning

confidence: 99%

“…the brain parenchyma. 5 In comparison, PDI is an indicator of particle size uniformity. Each of these features provides key insight to the nanoformulations we have access to that are stable, uniform, and can theoretically transport through the brain to areas of interest.…”

Section: Notesmentioning

confidence: 99%

“…4 Simultaneously, the brain microenvironment is heterogeneous from brain region to brain region, and dynamic during development, aging, and disease, which can affect nanomedicine delivery to the target destination. 5 The multitude of nanomedicine design parameters and neurobiological factors creates a large data space for which identification of key nanoparticle-brain interaction parameters is critical. To manage and query the large data space for nanoparticle-brain interactions, a nanoformulation database can assist in organizing and integrating key experimental variables that might influence the effectiveness of nanotherapeutics in the brain.…”

Section: Introductionmentioning

confidence: 99%

“…Nanomedicine physical and chemical characteristics such as size, charge, composition, and surface functionality impact interactions with cells, proteins, and extracellular components within the brain and ultimately the therapeutic effect 4 . Simultaneously, the brain microenvironment is heterogeneous from brain region to brain region, and dynamic during development, aging, and disease, which can affect nanomedicine delivery to the target destination 5 . The multitude of nanomedicine design parameters and neurobiological factors creates a large data space for which identification of key nanoparticle‐brain interaction parameters is critical.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Data management schema design for effective nanoparticle formulation for neurotherapeutics

Helmbrecht

Liao

et al. 2021

AIChE Journal

Self Cite

View full text Add to dashboard Cite

Translation of nanotherapeutics from preclinical research to clinical application is difficult due to the complex and dynamic interaction space between the nanotherapeutic and the brain environment. To improve translation, increased insight into nanoformulation-brain interactions in preclinical research is necessary. We developed a nanoformulation-brain database and wrote queries to connect the complex physical, chemical, and biological features of neurotherapeutics based on experimental data. We queried the database to select nanoformulations based on specific physical characteristics that enable effective penetration within the brain, including size, polydispersity index, and zeta potential. Additionally, we demonstrate the ability to query the database to return select nanoformulation characteristics, including nanoformulation methodology or methodological variables such as surfactant, polymer, drug loading, and sonication times. Finally, we show the capacity of our database to produce correlations relating nanoparticle formulation parameters to biological outcomes, including nanotherapeutic impact on cell viability in cultured brain slices.

show abstract

Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases

Yong,

Cai,

Lin

et al. 2024

Med-X

View full text Add to dashboard Cite

Cells in the brain are surrounded by extracellular space (ECS), which forms porous nets and interconnected routes for molecule transportation. Our view of brain ECS has changed from a largely static compartment to dynamic and diverse structures that actively regulate neural activity and brain states. Emerging evidence supports that dysregulation of brain ECS contributes to the pathogenesis and development of many neurological disorders, highlighting the importance of therapeutic modulation of brain ECS function. Here, we aim to provide an overview of the regulation and dysfunction of ECS in healthy and pathological brains, as well as advanced tools to investigate properties of brain ECS. This review emphasizes modulation methods to manipulate ECS with implications to restore their function in brain diseases. Graphical Abstract

show abstract

Governing transport principles for nanotherapeutic application in the brain

Cited by 8 publications

References 46 publications

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Data management schema design for effective nanoparticle formulation for neurotherapeutics

Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases

Contact Info

Product

Resources

About