Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target?

Kobayashi, Hisataka; Watanabe, Rira; Choyke, Peter L.

doi:10.7150/thno.7193

Cited by 855 publications

(599 citation statements)

References 70 publications

(70 reference statements)

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“…In addition, PCL NPs are larger than PLA NPs, which is in a good agreement with the dynamic light scattering data for the two polymers. When administrated intravenously, NPs should be sufficiently small (100-300 nm) to passively cross the tumor endothelial barrier and then retain in the tumor bed for prolonged time due to 22 reduced lymphatic drainage, which is known as the enhanced permeability and retention effect (Kobayashi et al, 2014). Particles larger than 1 µm are not convenient for intravascular delivery of drugs, since they can readily be opsonized with a possibility of capillary occlusion, while NPs smaller than 5 nm can be cleared rapidly from the blood via extravasation or renal clearance (Elsabahy and Wooley, 2012).…”

Section: Microscopic Images Of Npsmentioning

confidence: 99%

Preparation of biodegradable polymeric nanoparticles for pharmaceutical applications using glass capillary microfluidics

Othman

Vladisavljević

Nagy

2015

Chemical Engineering Science

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The aim of this study was to develop a new microfluidic approach for the preparation of nanoparticles with tuneable sizes based on micromixing / direct nanoprecipitation in a coaxial assembly of tapered-end glass capillaries. The organic phase was 1 wt% poly(-caprolactone) (PCL) or poly(dl-lactic acid) (PLA) in tetrahydrofuran and the antisolvent was Milli-Q water.The size of nanoparticles was precisely controlled over a range of 190-650 nm by controlling phase flow rates, orifice size and flow configuration (two-phase co-flow or countercurrent flow focusing). Smaller particles were produced in a flow focusing device, because the organic phase stream was significantly narrower than the orifice and remained narrow for a longer distance downstream of the orifice. The mean size of PCL particles produced in a flow focusing device with an orifice size of 200 m, an organic phase flow rate of 1.7 mL h -1 and an aqueous-toorganic flow rate ratio of 10 was below 200 nm. The size of nanoparticles decreased with decreasing the orifice size and increasing the aqueous-to-organic phase flow rate ratio. Due to *Revised Manuscript Click here to view linked References 2 higher affinity for water and amorphous structure, PLA nanoparticles were smaller and exhibited a smoother surface and more rounded shape than PCL particles.

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Section: Microscopic Images Of Npsmentioning

confidence: 99%

Preparation of biodegradable polymeric nanoparticles for pharmaceutical applications using glass capillary microfluidics

Othman

Vladisavljević

Nagy

2015

Chemical Engineering Science

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“…However, optimized size of liposomal formulation is a critical aspect in order to develop efficient therapeutics against glioma. It has been reported in the literature that a nanosize (5200 nm) drug carrier can exploit the advantages of leaky vasculature associated with primary brain cancer for transport of therapeutic payload within the tumor easily through a common mechanism known as enhanced permeability and retention effect (EPR) (Kobayashi et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor

et al. 2017

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Docetaxel (DTX) is found to be very effective against glioma cell in vitro. However, in vivo passage of DTX through BBB is extremely difficult due to the physicochemical and pharmacological characteristics of the drug. No existing formulation is successful in this aspect. Hence, in this study, effort was made to send DTX through blood-brain barrier (BBB) to brain to treat diseases such as solid tumor of brain (glioma) by developing DTX-loaded nanoliposomes. Primarily drug-excipients interaction was evaluated by FTIR spectroscopy. The DTX-loaded nanoliposomes (L-DTX) were prepared by lipid layer hydration technique and characterized physicochemically. In vitro cellular uptake in C6 glioma cells was investigated. FTIR data show that the selected drug and excipients were chemically compatible. The unilamellar vesicle size was less than 50 nm with smooth surface. Drug released slowly from L-DTX in vitro in a sustained manner. The pharmacokinetic data shows more extended action of DTX from L-DTX in experimental rats than the free-drug and Taxotere Õ . DTX from L-DTX enhanced 100% drug concentration in brain as compared with Taxotere Õ in 4 h. Thus, nanoliposomes as vehicle may be an encouraging strategy to treat glioma with DTX.

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“…33,34 The nontoxic and hydrophilic metal NPs could improve solubility issues and enhance tumor targeting due to the higher penetration and retention effects. 33,34 Hence, we also investigated and report herein the photooxidative capability of bio-SPIONs relative to HeLa cells.…”

Section: Introductionmentioning

confidence: 99%

Microwave-assisted green synthesis of superparamagnetic nanoparticles using fruit peel extracts: surface engineering, <em>T</em><sub>2</sub> relaxometry, and photodynamic treatment potential

Bano¹,

Nazir²,

Nazir³

et al. 2016

IJN

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Superparamagnetic iron oxide nanoparticles (SPIONs) have the potential to be used as multimodal imaging and cancer therapy agents due to their excellent magnetism and ability to generate reactive oxygen species when exposed to light. We report the synthesis of highly biocompatible SPIONs through a facile green approach using fruit peel extracts as the biogenic reductant. This green synthesis protocol involves the stabilization of SPIONs through coordination of different phytochemicals. The SPIONs were functionalized with polyethylene glycol (PEG)-6000 and succinic acid and were extensively characterized by X-ray diffraction analysis, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, Rutherford backscattering spectrometry, diffused reflectance spectroscopy, fluorescence emission, Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, and magnetization analysis. The developed SPIONs were found to be stable, almost spherical with a size range of 17–25 nm. They exhibited excellent water dispersibility, colloidal stability, and relatively high R 2 relaxivity (225 mM −1 s −1 ). Cell viability assay data revealed that PEGylation or carboxylation appears to significantly shield the surface of the particles but does not lead to improved cytocompatibility. A highly significant increase of reactive oxygen species in light-exposed samples was found to play an important role in the photokilling of human cervical epithelial malignant carcinoma (HeLa) cells. The bio-SPIONs developed are highly favorable for various biomedical applications without risking interference from potentially toxic reagents.

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Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target?

Cited by 855 publications

References 70 publications

Preparation of biodegradable polymeric nanoparticles for pharmaceutical applications using glass capillary microfluidics

Preparation of biodegradable polymeric nanoparticles for pharmaceutical applications using glass capillary microfluidics

Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor

Microwave-assisted green synthesis of superparamagnetic nanoparticles using fruit peel extracts: surface engineering, <em>T</em><sub>2</sub> relaxometry, and photodynamic treatment potential

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