Simulation study of the effects of interstitial fluid pressure and blood flow velocity on transvascular transport of nanoparticles in tumor microenvironment

Gao, Yan; Shi, Yanchao; Fu, Mengguang; Feng, Yu; Lin, Guimei; Kong, Deyin; Jiang, Bo

doi:10.1016/j.cmpb.2020.105493

Cited by 25 publications

(14 citation statements)

References 31 publications

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“…The results showed that the pressure at the vessel wall and the pressure gradient between the vascular wall and interstitial tissue increase in turn with the increase of fluid velocity in the vascular domain. Moreover, the trans-vascular transport efficiency of nanoparticles initially increases and subsequently decreases [114]. In addition, driven by the difference in pressure along the vascular direction, blood perfusion has the characteristics of convection-diffusion.…”

Section: Irregular Blood Flowmentioning

confidence: 99%

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Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

Dong

Sun

Huang

et al. 2021

JPM

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The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

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Section: Irregular Blood Flowmentioning

confidence: 99%

“…Nevertheless, antiangiogenic drugs also reduce the gap between tumor vascular ECs. Hence, the size of nanoparticles has to be strictly controlled if antiangiogenic drugs are employed to enhance the EPR effect [114].…”

Section: Antiangiogenesismentioning

confidence: 99%

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

Dong

Sun

Huang

et al. 2021

JPM

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“…A normalization of the blood flow velocity may help to recover a “normal” diffusion. Gao and his team ( Gao et al, 2020 ) have shown that an increase of blood flow velocity enhanced pressure gradient between vessels and interstitial tissue, thereby promoting diffusion of nanoparticles from the blood to the interstitial domain. On the opposite, interstitial fluid pressure in tumour microenvironment is higher than in normal tissue ( Gao et al, 2020 ; Wu et al, 2014 ).…”

Section: Extracellular Barriersmentioning

confidence: 99%

Therapeutic antibodies – natural and pathological barriers and strategies to overcome them

Ojaimi

Blin

Lamamy

et al. 2022

Pharmacology & Therapeutics

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Antibody-based therapeutics have become a major class of therapeutics with over 120 recombinant antibodies approved or under review in the EU or US. This therapeutic class has experienced a remarkable expansion with an expected acceleration in 2021–2022 due to the extraordinary global response to SARS-CoV2 pandemic and the public disclosure of over a hundred anti-SARS-CoV2 antibodies. Mainly delivered intravenously, alternative delivery routes have emerged to improve antibody therapeutic index and patient comfort. A major hurdle for antibody delivery and efficacy as well as the development of alternative administration routes, is to understand the different natural and pathological barriers that antibodies face as soon as they enter the body up to the moment they bind to their target antigen. In this review, we discuss the well-known and more under-investigated extracellular and cellular barriers faced by antibodies. We also discuss some of the strategies developed in the recent years to overcome these barriers and increase antibody delivery to its site of action. A better understanding of the biological barriers that antibodies have to face will allow the optimization of antibody delivery near its target. This opens the way to the development of improved therapy with less systemic side effects and increased patients’ adherence to the treatment.

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“…As we discussed previously, when the nanoparticle enters the bloodstream it encounters hydrodynamic forces and a corona of bloodstream proteins forms on its surface; a subset of these proteins form the highly specific complement activation reaction that leads to removal by macrophages. Regarding behavior in the bloodstream and the effect of size and shape (Shah et al, 2011), the most suitable method is not MD, but rather a combination of theoretical calculation (Decuzzi et al, 2005) and a discretized continuum model known as computational fluid dynamics (CFD), described and used to model this by Li et al (2014b), Gupta (2016), and Gao et al (2020) to model nanoparticle transport in the faulty tumor vasculature (Gao et al). As we have mentioned, the formation of the protein corona is an extremely complex process that still remains poorly understood.…”

Section: Insight Examples Behavior In the Bloodstream And Protectimentioning

confidence: 99%

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

Bunker

Róg

2020

Front. Mol. Biosci.

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In this review, we outline the growing role that molecular dynamics simulation is able to play as a design tool in drug delivery. We cover both the pharmaceutical and computational backgrounds, in a pedagogical fashion, as this review is designed to be equally accessible to pharmaceutical researchers interested in what this new computational tool is capable of and experts in molecular modeling who wish to pursue pharmaceutical applications as a context for their research. The field has become too broad for us to concisely describe all work that has been carried out; many comprehensive reviews on subtopics of this area are cited. We discuss the insight molecular dynamics modeling has provided in dissolution and solubility, however, the majority of the discussion is focused on nanomedicine: the development of nanoscale drug delivery vehicles. Here we focus on three areas where molecular dynamics modeling has had a particularly strong impact: (1) behavior in the bloodstream and protective polymer corona, (2) Drug loading and controlled release, and (3) Nanoparticle interaction with both model and biological membranes. We conclude with some thoughts on the role that molecular dynamics simulation can grow to play in the development of new drug delivery systems.

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Simulation study of the effects of interstitial fluid pressure and blood flow velocity on transvascular transport of nanoparticles in tumor microenvironment

Cited by 25 publications

References 31 publications

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

Therapeutic antibodies – natural and pathological barriers and strategies to overcome them

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

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