ApoE-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier

Magro, Roberta Dal; Ornaghi, Francesca; Cambianica, Ilaria; Beretta, Silvia; Re, Francesca; Musicanti, Claudia; Rigolio, R; Donzelli, E; Canta, A; Ballarini, E; Cavaletti, Guido; Gasco, Paolo; Sancini, Giulio

doi:10.1016/j.jconrel.2017.01.039

Cited by 128 publications

(80 citation statements)

References 57 publications

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“…Moreover, low PGZ concentrations produced NPs with greater negative ZP that could help prevent particle aggregation, thereby increasing the stability of the dispersion. 41 Importantly, the lower concentration of Tw also decreased the toxicity for hCMEC/D3 cells, besides facilitating interaction with endothelial surface molecules and hence, transport across the BBB. 42 Different kinetic models of drug release were tested with both formulations to select the best fit.…”

Section: Pgz Nanocarrier Characterization and Release Profilementioning

confidence: 98%

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

Silva-Abreu¹,

Calpena²,

Andrés‐Benito³

et al. 2018

IJN

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ObjectiveThe first aim of this study was to develop a nanocarrier that could transport the peroxisome proliferator-activated receptor agonist, pioglitazone (PGZ) across brain endothelium and examine the mechanism of nanoparticle transcytosis. The second aim was to determine whether these nanocarriers could successfully treat a mouse model of Alzheimer’s disease (AD).MethodsPGZ-loaded nanoparticles (PGZ-NPs) were synthesized by the solvent displacement technique, following a factorial design using poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG). The transport of the carriers was assessed in vitro, using a human brain endothelial cell line, cytotoxicity assays, fluorescence-tagged nanocarriers, fluorescence-activated cell sorting, confocal and transmission electron microscopy. The effectiveness of the treatment was assessed in APP/PS1 mice in a behavioral assay and by measuring the cortical deposition of β-amyloid.ResultsIncorporation of PGZ into the carriers promoted a 50x greater uptake into brain endothelium compared with the free drug and the carriers showed a delayed release profile of PGZ in vitro. In the doses used, the nanocarriers were not toxic for the endothelial cells, nor did they alter the permeability of the blood–brain barrier model. Electron microscopy indicated that the nanocarriers were transported from the apical to the basal surface of the endothelium by vesicular transcytosis. An efficacy test carried out in APP/PS1 transgenic mice showed a reduction of memory deficit in mice chronically treated with PGZ-NPs. Deposition of β-amyloid in the cerebral cortex, measured by immunohistochemistry and image analysis, was correspondingly reduced.ConclusionPLGA-PEG nanocarriers cross brain endothelium by transcytosis and can be loaded with a pharmaceutical agent to effectively treat a mouse model of AD.

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Section: Pgz Nanocarrier Characterization and Release Profilementioning

confidence: 98%

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

Silva-Abreu¹,

Calpena²,

Andrés‐Benito³

et al. 2018

IJN

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“…The cellular uptake was found to be higher in SLN-antibody conjugation than the normal SLN 67 . The surface modification of SLN with apolipoprotein E-derived peptide (SLN-mApoE) was efficiently crossed the blood-brain barrier when tested using in-vitro model by Dal et al The more confinement in the brain was found after pulmonary administration of SLN-mApoE, when compared to intravenous and intraperitoneal administration 68 . In a study, tocopherol succinate loaded SLN were developed for brain delivery of rivastigmine hydrogen tartrate for Alzheimer's disease.…”

Section: Sln For Brain Targeted Drug Deliverymentioning

confidence: 99%

Solid lipid nanoparticles: a promising technology for delivery of poorly water-soluble drugs

Bhatt¹,

Sharma²,

Singh³

et al. 2018

actapharm

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Oral administration of drugs having low water solubility is hampered by various enzymatic barriers present in gastrointestinal (GI) tract. Lipid nanoparticles based on solid matrix have emerged as a potential drug delivery system to improve the absorption and bioavailability of several drugs, especially lipophilic compounds. Solid lipid nanoparticles (SLN) are reported as the most promising technology for oral administration and offered several advantages over conventional dosages formulations including, enhancement in solubility, stability, permeability, and bioavailability with minimal side effects. In this review, we have highlighted recent advances in the development of SLN for the oral, parenteral, rectal, and topical administration of various drugs. We have also summarized the applications of SLN in the treatment of various diseases like tuberculosis, cancer, diabetes, and several nervous system related disorders. sustained release, timed release, extended release, and targeted release of a drug. The predominance of nanoparticles over the other drug delivery systems enables them to use for drug targeting. Nanoparticles are 10-100nm in size in which drug is either dispersed or entrapped in a matrix, encapsulated as the solid solution or may be adsorbed on the surface 2 .The nanoparticles are designed to provide intimate contact with GI epithelium, prolong residence time and allow permeation across the cell membrane. A pre-systemic metabolism of a drug can be avoided by using nanoparticles 3 . Lipid nanoparticles are safe to use as they contain lipids, which are included in the category of generally recognized as safe (GRAS). Solid Lipid NanoparticlesSolid lipid nanoparticles are an advanced and rapidly budding field of nanotechnology with several applications in pharmaceutical science. SLN were developed first in 1991. These are the colloidal carriers possesses an average diameter of 10 to 1000nm. They composed of single lipid core matrix dispersed in an aqueous surfactant solution. The carriers like liposomes, polymeric micelles, and porous solids can also be used to enhance the aqueous solubility of a drug. But SLN not only helps to increase the solubility of a drug but also offers target release of drugs. SLN can be used as a carrier for lipophilic as well as hydrophilic drugs 4 . SLN provides stability to the solid lipid matrix and overcomes the disadvantages of liposomes, which includes stability problems 5 . Instead of polymeric nanoparticles, SLN are found to be more compatible with the biological system. Exclusive properties of SLN such as smaller size, larger surface area and interaction of phases at the interface make them valuable candidate 2 . The release of encapsulated compounds is controlled by solid lipid matrix, which also improves the stability of incorporated lipophilic ingredients. The type of lipids, surfactants and their concentration in the formulation of SLN adjust the particle size, drug loading, and release behavior of drugs 5 . The physicochemical characteristics of the solid lipid...

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“…Generally, size of nanomedicine is in the range of 50-200 nm, which however, is too large to cross BBB through free diffusion [19]. To address the issue, outer surface of NPs is further engineered with various targeting ligands that mimic endogenous substances, and thus, gain access to brain parenchyma using receptor-mediated endocytosis [20]. It is predicted that nanomedicine can deliver entrapped drug in to the brain parenchyma at least in two ways; a.…”

Section: Nanomedicine: Trojan-horse To Brain Drug Deliverymentioning

confidence: 99%

“…In a recent study, solid-lipid nanoparticles decorated with human apolipoprotein E (ApoE) were evaluated for their adaptability to surpass BBB. The administration of nanomedicine via pulmonary route demonstrated improved bioavailability, compared with unmodified counterpart [20].…”

Section: Nanomedicine: Trojan-horse To Brain Drug Deliverymentioning

confidence: 99%

The Significance of Nanomedicine in Brain-Targeted Drug Delivery: Crossing Blood-Brain Barriers

Singh¹

2017

JNMR

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At present, the brain ailments are among the most complex disease to treat since therapies are strictly hindered through the highly selective blood-brain barrier (BBB). The efficacy of CNS acting therapeutics is determined by their ability to cross the BBB at therapeutic dose. Therefore, there is an urgent need for strategies that enable CNS therapeutic to cross BBB effectively hitherto frozen mainly of BBB. The nanomedicine represents a cutting edge tool in the field of biomedicine and promising addition to the spectrum of brain-targeted drug delivery. The promises revolve around the biocompatibility and unique versatility of site-specific drug delivery. A broad variety of CNS acting therapeutics can be entrapped in polymeric matrix, which further can be surface engineered with brain-specific ligands to facilitate the delivery of therapeutics across BBB. The scope of this communication presents recent advancements in the field of nanomedicine in context to brain-targeted drug delivery, with an eye toward the opportunity for translation from bench to bedside.

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ApoE-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier

Cited by 128 publications

References 57 publications

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

Solid lipid nanoparticles: a promising technology for delivery of poorly water-soluble drugs

The Significance of Nanomedicine in Brain-Targeted Drug Delivery: Crossing Blood-Brain Barriers

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ApoE-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier

Cited by 128 publications

References 57 publications

PPAR&gamma; agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer&rsquo;s disease: in vitro and in vivo studies

PPAR&gamma; agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer&rsquo;s disease: in vitro and in vivo studies

Solid lipid nanoparticles: a promising technology for delivery of poorly water-soluble drugs

The Significance of Nanomedicine in Brain-Targeted Drug Delivery: Crossing Blood-Brain Barriers

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Product

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PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies