Influence of nanoparticle size on blood–brain barrier penetration and the accumulation of anti-seizure medicines in the brain

Qian, Meng; Meng, Hongmei; Pan, Yong; Liu, Jiayu; Li, Jiaai; Qi, Yanxin; Huang, Yubin

doi:10.1039/d1tb02015c

Cited by 42 publications

(15 citation statements)

References 53 publications

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“…As the size of the nanoparticle increases, its chance to cross the blood-brain barrier (BBB) decreases. In the other words, smaller particles have a higher chance to accumulate, penetrate, and internalize effectively into the brain compared to larger ones [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery

Mozafari

Rashidzadeh

Bijani

et al. 2023

Oxidative Medicine and Cellular Longevity

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Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. In vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage.

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Section: Discussionmentioning

confidence: 99%

Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery

Mozafari

Rashidzadeh

Bijani

et al. 2023

Oxidative Medicine and Cellular Longevity

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“…Size effect is an essential factor that needs to be considered when designing NPs because it will directly affect their uptake and permeability through the BBB. NPs of different sizes show diverse circulation half-life time, vascular permeability, and macrophage clearance 149 and have different tendencies to accumulate in different organs. For instance, NPs smaller than 5 nm in diameter could cross the BBB effortlessly.…”

Section: Size Effect Of Nanoparticlesmentioning

confidence: 99%

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Zha,

Liu,

et al. 2024

ACS Nano

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The blood−brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.

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“…We next examined whether physical characteristics of the LNPs correlated with transport performance since there has been extensive prior research examining the effect of nanoparticle size on transport. Examples include studying polystyrene and protein-based nanoparticles, gold nanoparticles, and PEG–PLGA nanoparticles . Size and zeta potential of the LNPs did not correlate with transport performance, potentially indicating that other LNP properties such as lipid structures may play a bigger role in transport (Figure S10).…”

Section: Screening a Library Of Lnps With Unique Ionizable Lipids In ...mentioning

confidence: 99%

Predictive High-Throughput Platform for Dual Screening of mRNA Lipid Nanoparticle Blood–Brain Barrier Transfection and Crossing

Han,

Padilla,

Palanki

et al. 2024

Nano Lett.

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Lipid nanoparticle (LNP)-mediated nucleic acid therapies, including mRNA protein replacement and gene editing therapies, hold great potential in treating neurological disorders including neurodegeneration, brain cancer, and stroke. However, delivering LNPs across the blood−brain barrier (BBB) after systemic administration remains underexplored. In this work, we engineered a high-throughput screening transwell platform for the BBB (HTS-BBB), specifically optimized for screening mRNA LNPs. Unlike most transwell assays, which only assess transport across an endothelial monolayer, HTS-BBB simultaneously measures LNP transport and mRNA transfection of the endothelial cells themselves. We then use HTS-BBB to screen a library of 14 LNPs made with structurally diverse ionizable lipids and demonstrate it is predictive of in vivo performance by validating lead candidates for mRNA delivery to the mouse brain after intravenous injection. Going forward, this platform could be used to screen large libraries of brain-targeted LNPs for a range of protein replacement and gene editing applications.

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Influence of nanoparticle size on blood–brain barrier penetration and the accumulation of anti-seizure medicines in the brain

Abstract: Anti-seizure medicines constitute a common yet important modality to treat epilepsy. However, some of them are associated with serious side effects including hepatotoxicity and hypersensitivity. Furthermore, the blood-brain barrier (BBB)...

Cited by 42 publications

References 53 publications

Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery

Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Predictive High-Throughput Platform for Dual Screening of mRNA Lipid Nanoparticle Blood–Brain Barrier Transfection and Crossing

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