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Calvo, Pilar; Gouritin, Bruno; Chacun, Hélène; Desmaële, Didier; d’Angelo, Jean; Noël, Jean‐Pierre; Georgin, Dominique; Fattal, Elias; Andreux, J.P.; Couvreur, Patrick

doi:10.1023/a:1010931127745

Cited by 407 publications

(118 citation statements)

References 23 publications

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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%

“…PEGylated materials evade the MPS, enhancing bioavailability, and possess the ability to cross the BBB, for which the exact mechanism is unknown but could include transcytosis or receptor-mediated endocytosis [15]. PEG-coated nanoparticles accumulate in brain tissue more effectively than non-PEG-coated nanoparticles, and those coated with high density PEG also display greater diffusion through brain parenchyma [4,16]. Of high relevance for clinical applications, PEG-coated nanoparticle accumulation is enhanced in pathological foci including gliosarcoma and Multiple Sclerosis models [17,18], possibly due to inflammation-induced BBB hyperpermeability -similar to enhanced nanoparticle permeability/retention (EPR effect) in brain tumors [19].…”

Section: Introductionmentioning

confidence: 99%

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‘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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Section: Introductionmentioning

confidence: 99%

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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“…[10][11][12][13] Several nanoparticles have been reported to accumulate in the CNS, thus suggesting their ability to cross the BBB. [14][15][16] However the mechanisms still remain unclear and direct evidence of transcytosis in vivo has not been generated as yet. These observations have raised safety concerns due to the increased exposure of organisms and humans to nanoparticulate matter.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

et al. 2013

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The Blood-Brain Barrier (BBB) is a selective barrier, which controls and limits access to the central nervous system (CNS). The selectivity of the BBB relies on specialized characteristics of the endothelial cells that line the microvasculature, including the expression of intercellular tight junctions, which limit paracellular permeability. Several reports suggest that nanoparticles have a unique capacity to cross the BBB. However, direct evidence of nanoparticle transcytosis is difficult to obtain, and we found that typical transport studies present several limitations when applied to nanoparticles. In order to investigate the capacity of nanoparticles to access and transport across the BBB, several different nanomaterials, including silica, titania and albumin-or transferrinconjugated gold nanoparticles of different sizes, were exposed to a human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission electron microscopy imaging was applied in order to describe nanoparticle endocytosis and typical intracellular localisation, as well as to look for evidence of eventual transcytosis. Our results show that all of the nanoparticles were internalised, to different extents, by the BBB model and accumulated along the endo-lysosomal pathway. Rare events suggestive of nanoparticle transcytosis were also observed for several of the tested materials.

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“…27) The particle size of nanoparticles is an important property to control the endocytosis rate across the brain capillary endothelial cells. 29,30) All the formulated batches had an average diameter in the nanometer range varying from 155.5 to 636 nm ( Table 2). The particle size was found to increase with increasing drug: polymer ratio which could be attributed to the amount of polymer that was enough to maintain the stability of nanoparticles at equal molar ratio of drug and polymer and coalescence of droplet did not occur at this ratio.…”

Section: Discussionmentioning

confidence: 99%

Formulation, Optimization, <i>in Vivo</i> Pharmacokinetic, Behavioral and Biochemical Estimations of Minocycline Loaded Chitosan Nanoparticles for Enhanced Brain Uptake

Nagpal

Singh

Mishra

2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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The minocycline hydrochloride (MH), at higher doses, is useful in the treatment of neurodegenerative disorders and owing to its antioxidant potential, it may have nootropic effects. MH loaded nanoparticles (MHNP) were coated with tween 80 (cMHNP) to improve its brain uptake followed by their optimization employing two factor-three level (3 2 ) central composite design (CCD) in order to minimize particle size and maximize drug entrapment efficiency (DEE) and validated. The optimized formulations were further subjected to in vitro drug release study; in vivo biodistribution studies in male wistar rats. The pharmacodynamic study was carried out using elevated plus maze (EPM) and Morris water maze (MWM) behavioral models for nootropic activity in swiss albino mice; and biochemical estimations (acetylcholine esterase, reduced glutathione, malondialdehyde and brain nitrite level). After intravenous (i.v.) administration, the concentration of MH in brain of cMHNP (6.21±0.64 µg/mL) treated rats was significantly higher with MH solution treated (0.70±0.06 µg/mL) as well as MHNP (1.03±0.12 µg/mL) treated animals. Pharmacodynamic studies revealed a significant improvement in memory of MH, MHNP and cMHNP treated swiss albino mice than saline treated control group. However, cMHNP revealed maximum decrease in transfer latency (TL) in EPM and maximum increase in time spent in target quadrant (TSTQ) in MWM. Although cMHNP did not produce significant change in brain acetylcholinesterase, but, significantly increased reduced glutathione, malondialdehyde and reduced brain nitrite level as compared to saline, MH solution and MHNP treated groups. The results suggest that cMHNP is a promising candidate for improved brain uptake of MH with better no o tro pic effect.

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Cited by 407 publications

References 23 publications

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

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

Nanoparticle accumulation and transcytosis in brain endothelial cell layers

Formulation, Optimization, <i>in Vivo</i> Pharmacokinetic, Behavioral and Biochemical Estimations of Minocycline Loaded Chitosan Nanoparticles for Enhanced Brain Uptake

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