Blood–brain barrier models and their relevance for a successful development of CNS drug delivery systems: A review

Bicker, Joana; Alves, Gilberto; Fortuna, Ana

doi:10.1016/j.ejpb.2014.03.012

Cited by 225 publications

(164 citation statements)

References 268 publications

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“…In vitro studies using human cells therefore represent a useful alternative approach, yet most studies of cerebrovascular function use monotypic cultures of brain ECs, which do not mimic the complexity of cell-cell and/or cell-matrix interactions found in the native vessel. As an improvement, EC and astrocytes, EC and SMC, and EC and pericytes have been co-cultured, however, this is almost always under static culture conditions (Di et al, 2009;Cho et al, 2007;Bicker et al, 2014;Navone et al, 2013;Man et al, 2008;Hatherell et al, 2011;Bussolari et al, 1982;Cucullo et al, 2007). More recent studies developed an EC and astrocyte co-culture model using a complex flow system, but this model did not allow histological analysis or cell-ECM interactions to be assessed (Cucullo et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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Amyloid plaques, consisting of deposited beta-amyloid (Ab), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Ab is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Ab transport across bioengineered human cerebral vessels. These lipoproteins facilitate Ab42 transport more efficiently than Ab40, consistent with Ab40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Ab transport, also consistent with the well-established role of apoE4 in Ab deposition in AD.

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Section: Discussionmentioning

confidence: 99%

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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“…87 Several synthetic drugs are used to prepare solid lipid nanoparticles to prevent various conditions in PD. [88][89][90][91] Bromocriptine-loaded solid lipid nanoparticles have been developed and studied in patients with PD and are highly effective in reducing dyskenesia. 88 However, nanophytobioactive compounds developed using a solid lipid nanoparticle delivery system showed higher bioavailability.…”

Section: Ganesan Et Almentioning

confidence: 99%

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

Ganesan¹,

Ko²,

Kim³

et al. 2015

IJN

105

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Oxidative stress plays a very critical role in neurodegenerative diseases, such as Parkinson’s disease (PD), which is the second most common neurodegenerative disease among elderly people worldwide. Increasing evidence has suggested that phytobioactive compounds show enhanced benefits in cell and animal models of PD. Curcumin, resveratrol, ginsenosides, quercetin, and catechin are phyto-derived bioactive compounds with important roles in the prevention and treatment of PD. However, in vivo studies suggest that their concentrations are very low to cross blood–brain barrier thereby it limits bioavailability, stability, and dissolution at target sites in the brain. To overcome these problems, nanophytomedicine with the controlled size of 1–100 nm is used to maximize efficiency in the treatment of PD. Nanosizing of phytobioactive compounds enhances the permeability into the brain with maximized efficiency and stability. Several nanodelivery techniques, including solid lipid nanoparticles, nanostructured lipid carriers, nanoliposomes, and nanoniosomes can be used for controlled delivery of nanobioactive compounds to brain. Nanocompounds, such as ginsenosides (19.9 nm) synthesized using a nanoemulsion technique, showed enhanced bioavailability in the rat brain. Here, we discuss the most recent trends and applications in PD, including 1) the role of phytobioactive compounds in reducing oxidative stress and their bioavailability; 2) the role of nanotechnology in reducing oxidative stress during PD; 3) nanodelivery systems; and 4) various nanophytobioactive compounds and their role in PD.

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“…However, in vivo models are often low-throughput, expensive, and labour-intensive, and there are no in vitro models that can mimic all of the properties of the in vivo BBB. The development of more reliable HTS models remains a challenge (Bicker et al 2014).…”

Section: Blood-brain Barrier (Bbb)mentioning

confidence: 99%

“…Among these methods, in vivo brain uptake experiments, including non-invasive and invasive techniques, provide the most reliable evaluation of BBB penetration. The key concepts that are used to estimate BBB permeability among in vivo experiments include the rate and extent of brain permeation, which are expressed as log PS (logarithm of the permeable-surface area product) and log BB (logarithm of the brain/blood partitioning ratio at a steady-state), respectively (Bicker et al 2014). Log BB is by far the most frequently used parameter for evaluating BBB penetration (Lanevskij et al 2013).…”

Section: Blood-brain Barrier (Bbb)mentioning

confidence: 99%

In silicoADME/T modelling for rational drug design

Wang

Xing

Yue

et al. 2015

Quart. Rev. Biophys.

277

155

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Abstract. In recent decades, in silico absorption, distribution, metabolism, excretion (ADME), and toxicity (T) modelling as a tool for rational drug design has received considerable attention from pharmaceutical scientists, and various ADME/T-related prediction models have been reported. The high-throughput and low-cost nature of these models permits a more streamlined drug development process in which the identification of hits or their structural optimization can be guided based on a parallel investigation of bioavailability and safety, along with activity. However, the effectiveness of these tools is highly dependent on their capacity to cope with needs at different stages, e.g. their use in candidate selection has been limited due to their lack of the required predictability. For some events or endpoints involving more complex mechanisms, the current in silico approaches still need further improvement. In this review, we will briefly introduce the development of in silico models for some physicochemical parameters, ADME properties and toxicity evaluation, with an emphasis on the modelling approaches thereof, their application in drug discovery, and the potential merits or deficiencies of these models. Finally, the outlook for future ADME/T modelling based on big data analysis and systems sciences will be discussed.

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Blood–brain barrier models and their relevance for a successful development of CNS drug delivery systems: A review

Cited by 225 publications

References 268 publications

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

In silicoADME/T modelling for rational drug design

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Blood–brain barrier models and their relevance for a successful development of CNS drug delivery systems: A review

Cited by 225 publications

References 268 publications

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson&rsquo;s disease models

In silicoADME/T modelling for rational drug design

Contact Info

Product

Resources

About

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models