Challenges in drug delivery to the brain: Nature is against us

Krol, Silke

doi:10.1016/j.jconrel.2012.04.044

Cited by 134 publications

(72 citation statements)

References 114 publications

(165 reference statements)

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“…Aside from intracellular accumulation, there was also evidence that different metal oxide NPs affect the membrane potentials of neurons and increase the neuronal firing rate by changing the responses of the potassium channels. 90 This finding was consistent with a toxicity study of nano-CuO on CA1 hippocampal neurons performed by Xu et al 123 Furthermore, this toxic effect may have a physiological impact on animal behavior, which was demonstrated in rats by testing their spatial cognition capabilities. 81 Recently, the impact of nanomaterials on the CNS, particularly the hippocampal neuronal cells, has been illustrated in a comprehensive review by Yang et al 124 …”

Section: Neurotoxicity On Neuronssupporting

confidence: 88%

“…In the brain, the NPs are in contact with three different cell types 90 : (1) BBB (specialized endothelium) and/or bloodliquid barrier cells (choriplexus endothelium between blood and CSF); (2) glial cells or neuroglia (macroglia: astrocytes and oligodendrocytes; microglia: pericytes regulating BBB functionality) 91 and precursors for macrophage-like cells; and (3) two general types of neurons (with [white matter] or without [gray matter] a myelin sheath). Different cell models will be described in this section, and key examples are given in Table 3.…”

Section: Neurotoxicity Of Nanomaterials On In Vitro Cellsmentioning

confidence: 99%

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Application of dental nanomaterials: potential toxicity to the central nervous system

Feng¹,

Chen²,

Wang³

et al. 2015

IJN

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Nanomaterials are defined as materials with one or more external dimensions with a size of 1–100 nm. Such materials possess typical nanostructure-dependent properties (eg, chemical, biological, optical, mechanical, and magnetic), which may differ greatly from the properties of their bulk counterparts. In recent years, nanomaterials have been widely used in the production of dental materials, particularly in light polymerization composite resins and bonding systems, coating materials for dental implants, bioceramics, endodontic sealers, and mouthwashes. However, the dental applications of nanomaterials yield not only a significant improvement in clinical treatments but also growing concerns regarding their biosecurity. The brain is well protected by the blood–brain barrier (BBB), which separates the blood from the cerebral parenchyma. However, in recent years, many studies have found that nanoparticles (NPs), including nanocarriers, can transport through the BBB and locate in the central nervous system (CNS). Because the CNS may be a potential target organ of the nanomaterials, it is essential to determine the neurotoxic effects of NPs. In this review, possible dental nanomaterials and their pathways into the CNS are discussed, as well as related neurotoxicity effects underlying the in vitro and in vivo studies. Finally, we analyze the limitations of the current testing methods on the toxicological effects of nanomaterials. This review contributes to a better understanding of the nano-related risks to the CNS as well as the further development of safety assessment systems.

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Section: Neurotoxicity On Neuronssupporting

confidence: 88%

Section: Neurotoxicity Of Nanomaterials On In Vitro Cellsmentioning

confidence: 99%

Application of dental nanomaterials: potential toxicity to the central nervous system

Feng¹,

Chen²,

Wang³

et al. 2015

IJN

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“…Nanoparticle delivery to the central nervous system (CNS) represents a critical biological challenge in this context [3]. Direct nanoparticle delivery to the CNS via intracerebral, intraventricular and intrathecal routes can produce high doses near target sites, but involves risk of clinical complications including embolism and haemorrhage [4].…”

Section: Introductionmentioning

confidence: 99%

“…insulin, leptin) into and out of the CNS [8]. This highly selective BBB restricts access of most therapeutic agents to the brain parenchyma [3,9].…”

Section: Introductionmentioning

confidence: 99%

‘Stealth’ nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics

Jenkins

Weinberg

al-Shakli

et al. 2016

Journal of Controlled Release

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“…Lecithin, a natural emulsifier, which mimics the biological system in the brain either by electrostatic or by covalent binding, is known to help particles cross the blood-brain barrier. 21 However, lecithin by itself was not enough to form a good nanoemulsion system. It has been reported that the usage of lecithin as an emulsifier may lead to the formation of lysoderivatives.…”

mentioning

confidence: 99%

Enhancement of encapsulation efficiency of nanoemulsion-containing aripiprazole for the treatment of schizophrenia using mixture experimental design

Masoumi¹,

Basri²,

Samiun³

et al. 2015

IJN

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Aripiprazole is considered as a third-generation antipsychotic drug with excellent therapeutic efficacy in controlling schizophrenia symptoms and was the first atypical anti-psychotic agent to be approved by the US Food and Drug Administration. Formulation of nanoemulsion-containing aripiprazole was carried out using high shear and high pressure homogenizers. Mixture experimental design was selected to optimize the composition of nanoemulsion. A very small droplet size of emulsion can provide an effective encapsulation for delivery system in the body. The effects of palm kernel oil ester (3–6 wt%), lecithin (2–3 wt%), Tween 80 (0.5–1 wt%), glycerol (1.5–3 wt%), and water (87–93 wt%) on the droplet size of aripiprazole nanoemulsions were investigated. The mathematical model showed that the optimum formulation for preparation of aripiprazole nanoemulsion having the desirable criteria was 3.00% of palm kernel oil ester, 2.00% of lecithin, 1.00% of Tween 80, 2.25% of glycerol, and 91.75% of water. Under optimum formulation, the corresponding predicted response value for droplet size was 64.24 nm, which showed an excellent agreement with the actual value (62.23 nm) with residual standard error <3.2%.

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Challenges in drug delivery to the brain: Nature is against us

Cited by 134 publications

References 114 publications

Application of dental nanomaterials: potential toxicity to the central nervous system

Application of dental nanomaterials: potential toxicity to the central nervous system

‘Stealth’ nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics

Enhancement of encapsulation efficiency of nanoemulsion-containing aripiprazole for the treatment of schizophrenia using mixture experimental design

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