Predicting drug delivery efficiency into tumor tissues through molecular simulation of transport in complex vascular networks

Troendle, Evan P.; Khan, Ayesha; Searson, Peter C.; Ulmschneider, Martin B.

doi:10.1016/j.jconrel.2018.11.010

Cited by 16 publications

(8 citation statements)

References 71 publications

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“…The tumor model is a representative model for studying NP accumulation in target tissue [63,69,147,148,149,150]. The 3D culture configuration in cancer research has shown higher drug resistance and more biomimicry than 2D culture [63,64], and tumor spheroids are currently the most popular models for cancer research due to their 3D configuration, reproducibility and ease of production.…”

Section: Key Microfluidic Models For Np Evaluationmentioning

confidence: 99%

Evaluating Nanoparticles in Preclinical Research Using Microfluidic Systems

Zhu

Long

et al. 2019

Micromachines

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Nanoparticles (NPs) have found a wide range of applications in clinical therapeutic and diagnostic fields. However, currently most NPs are still in the preclinical evaluation phase with few approved for clinical use. Microfluidic systems can simulate dynamic fluid flows, chemical gradients, partitioning of multi-organs as well as local microenvironment controls, offering an efficient and cost-effective opportunity to fast screen NPs in physiologically relevant conditions. Here, in this review, we are focusing on summarizing key microfluidic platforms promising to mimic in vivo situations and test the performance of fabricated nanoparticles. Firstly, we summarize the key evaluation parameters of NPs which can affect their delivery efficacy, followed by highlighting the importance of microfluidic-based NP evaluation. Next, we will summarize main microfluidic systems effective in evaluating NP haemocompatibility, transport, uptake and toxicity, targeted accumulation and general efficacy respectively, and discuss the future directions for NP evaluation in microfluidic systems. The combination of nanoparticles and microfluidic technologies could greatly facilitate the development of drug delivery strategies and provide novel treatments and diagnostic techniques for clinically challenging diseases.

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Section: Key Microfluidic Models For Np Evaluationmentioning

confidence: 99%

Evaluating Nanoparticles in Preclinical Research Using Microfluidic Systems

Zhu

Long

et al. 2019

Micromachines

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“…These properties limit the extravasation and penetration of the liposomes. Several system-based models have been proposed to analyze the impact of tumor vasculature and physical properties on heterogeneity in spatial distribution [95,124,125,126].…”

Section: The Application Of Pharmacokinetic–pharmacodynamic Modelimentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics Modeling and Simulation Systems to Support the Development and Regulation of Liposomal Drugs

Yuan

et al. 2019

Pharmaceutics

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Liposomal formulations have been developed to improve the therapeutic index of encapsulated drugs by altering the balance of on- and off-targeted distribution. The improved therapeutic efficacy of liposomal drugs is primarily attributed to enhanced distribution at the sites of action. The targeted distribution of liposomal drugs depends not only on the physicochemical properties of the liposomes, but also on multiple components of the biological system. Pharmacokinetic–pharmacodynamic (PK–PD) modeling has recently emerged as a useful tool with which to assess the impact of formulation- and system-specific factors on the targeted disposition and therapeutic efficacy of liposomal drugs. The use of PK–PD modeling to facilitate the development and regulatory reviews of generic versions of liposomal drugs recently drew the attention of the U.S. Food and Drug Administration. The present review summarizes the physiological factors that affect the targeted delivery of liposomal drugs, challenges that influence the development and regulation of liposomal drugs, and the application of PK–PD modeling and simulation systems to address these challenges.

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“…The transport of dispersion systems, like emulsions or suspensions, especially in small, micro-or nano-structures, plays a fundamental role in many fields of science and industry, such as, inter alia, medicine, the pharmaceutical industry, cosmetic, or the oil extracting industry (Lopes et al 2020;Rahman et al 2020;Shui et al 2007;Shah et al 2021;Scheffer et al 2021). Knowledge of the transport mechanisms of such liquids in microstructures is important when analyzing the movement of various types of particles or droplets through the circulatory system, including blood cells or cholesterol particles or even drugs introduced into the regime (Ohkawa et al 2020;Troendle et al 2018). It becomes important to estimate how fast these media will flow, how the speed will depend on their size or shape, where they will stop, and how they will affect the movement of other components.…”

Section: Introductionmentioning

confidence: 99%

Analysis of droplet displacement during transport of polydisperse emulsion as drug carriers in microchannels

Błaszczyk

Sęk

Przybysz

2022

Microfluid Nanofluid

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Drug transport in human body is often intensified by various carriers. The simplest and highly effective are emulsions. In these liquids, one phase is dispersed in other in the form of droplets, in which active substance is often dissolved. In existing application of such liquids as carriers, monodispersity of such systems has been a very important parameter, because when all droplets have same size, it is relatively easy to predict drug release time. However, monodisperse emulsion production on an industrial scale is expensive and technologically quite difficult. Therefore, it would be more reasonable to use polydisperse emulsions. However, mechanism of drug release from such carriers is more complicated and difficult to conduct. When emulsion droplets of different sizes pass through microchannels, i.e., blood vessels, individual droplets’ transport velocity is different and interdependent. The ability to predict rate at which individual droplets travel through microchannels will enable control of drug release depending on emulsion parameters. This work presents a detailed analysis of polydisperse emulsion transport through a single microchannel. Dependence of individual droplets velocity on their diameter and position relative to flow axis and influence of these parameters on droplet transport trajectories were studied. These studies were conducted for five liquid flow rates and three emulsion concentrations. As a result of this work, some generalization approach was proposed to estimate droplet transport velocity depending on their position in channel based on reference to single-phase flow. This work may find application in pharmaceutical industry for design of cheaper drug manufacturing technologies. Graphical abstract

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Predicting drug delivery efficiency into tumor tissues through molecular simulation of transport in complex vascular networks

Cited by 16 publications

References 71 publications

Evaluating Nanoparticles in Preclinical Research Using Microfluidic Systems

Evaluating Nanoparticles in Preclinical Research Using Microfluidic Systems

Pharmacokinetics and Pharmacodynamics Modeling and Simulation Systems to Support the Development and Regulation of Liposomal Drugs

Analysis of droplet displacement during transport of polydisperse emulsion as drug carriers in microchannels

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