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Engineered Nanoparticles for Drug Delivery in Cancer Therapy *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Tianmeng Sun, Yu Shrike Zhang, Pang Bo, Dong Choon Hyun, Miaoxin Yang, Younan Xia
Besides the efforts on nanoparticles themselves, it is of tremendous importance to develop realistic in vitro testing platforms that can effectively evaluate the performance of nanoparticle-based drug delivery systems. To date, the majority of the delivery systems work well in vitro, but fail when they are tested in the much more complicated in vivo microenvironment. Pronounced differences lie between in vitro tumor models and preclinical models (i.e., small or large laboratory animals), and between animals and human bodies. Over the past decade, three-dimensional (3D) culture systems based on porous scaffolds or hydrogels have gradually replaced the conventional two-dimensional (2D) cultures on plastic tissue culture plates (TCPs) in an effort to better mimic the in vivo organization of tissues. More comfortingly, a novel and exciting concept termed “organ-on-a-chip” was proposed a couple of years ago by Ingber and coworkers based on the pioneering work conducted by their own and Schuler’s group [337]. In such an approach, 3D miniaturized in vitro human tissues/organs (e.g., liver, lung, heart, kidney, and blood vessels) are created from perfusion cultures on microfluidic chips, and connected to each other to form a multiorgan, human-mimicry platform that can be used for testing drugs and nanoparticles. Using this “organ-on-a-chip” platform, one can conduct a more effective evaluation of the nanoparticles as drug delivery systems and thus predict their in vivo behaviors. Importantly, because of the “humanized” feature of the platform, it is expected that preclinical models might be eventually eliminated.
3D models as tools for inhaled drug development
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Sally-Ann Cryan, Jennifer Lorigan, Cian O’Leary
In the past few years, research into the organ-on-a-chip microfluidic platform technology has significantly expanded. Novel microfluidic approaches have led to the creation of lung-on-a-chip technology to model the bronchoalveolar region. Chip platforms are microengineered biomimetic systems that represent key functional units of living human organs. They often consist of transparent 3D polymeric microchannels lined by living human cells and replicate three important aspects of intact organs: the 3D microarchitecture defined by the spatial distribution of multiple tissue types; functional tissue–tissue interfaces; and complex organ-specific mechanical and biochemical microenvironments, as reviewed in (109). As such, these systems are more integrated than the 2D models because they provide more detailed information about inflammatory responses and drug uptake (110,111).
Determination of Toxicity
Published in David Woolley, Adam Woolley, Practical Toxicology, 2017
The use of culture methods to produce blocks of cells that have some of the characteristics of the original tissue is also a technique with considerable potential. Hepatocytes can be induced to maintain functionality for several weeks when mounted in an appropriate matrix of collagenous material. With the development of the concept of organ-on-a-chip, followed by the related human or body on a chip and the use of microtissue samples and microfluidics, the potential to explore the interrelationships of organs in vitro is becoming more practicable.
Critical design parameters to develop biomimetic organ-on-a-chip models for the evaluation of the safety and efficacy of nanoparticles
Published in Expert Opinion on Drug Delivery, 2023
Mahmoud Abdelkarim, Luis Perez-Davalos, Yasmin Abdelkader, Amr Abostait, Hagar I. Labouta
Several factors must be considered in the design of the organ-on-a-chip device that helps to mimic the physiological environment of the organ. The dimensions of the channels play a pivotal role in terms of mechanical forces applied inside the microchannel, which aid in making the shear stress uniform inside the channel along with the drag forces that affect the particles present during the fluid flow. Further, adjusting the aspect ratio of the microchannel would change the channel hydraulic resistance and thus affect the pressure drop along the channel. On the other hand, the shape of the channel affects the mechanical forces acting on the cells, whether it is a simple or complex microchannel structure. We, therefore, submit that future studies should first conduct computer simulations to optimize the chip design with the desired mechanical forces (the shear stress, shear rate, pressure … etc.).
Acute radiation syndrome drug discovery using organ-on-chip platforms
Published in Expert Opinion on Drug Discovery, 2022
Vijay K. Singh, Thomas M. Seed
Select pharmaceutical companies have a vested interest in developing more efficient and cost-effective MCM screening and testing systems. The organ-on-a-chip technologies can often emulate human physiology and functionality of specific organ systems and are amendable for disease and injury modeling and for MCM development. The in vitro 2D or 3D culture and various animal models are often less than optimal in terms of efficiency and precision testing. In this regard, animal models are the gold standard for the preclinical studies of pharmaceutical agents under development, but reproducibility of results and accuracy of findings are often undermined by response differences between species, i.e. not only in the responses noted between various animal species/models, but also between humans as well. As a result, ~40% of drugs fail clinical trials after prolonged preclinical investigation in various animal models [1]. The organ-on-chip technology can play an important role during different preclinical stages of MCM development, which may lead to a paradigm shift in pharmaceutical development and personalized medicine.
Real-time quantitative monitoring of in vitro nasal drug delivery by a nasal epithelial mucosa-on-a-chip model
Published in Expert Opinion on Drug Delivery, 2021
Hanieh Gholizadeh, Hui Xin Ong, Peta Bradbury, Agisilaos Kourmatzis, Daniela Traini, Paul Young, Ming Li, Shaokoon Cheng
Organ-on-chip technology has enhanced in vitro studies of drugs by providing physiologically relevant microenvironments that closely match the corresponding organs of interest, with the ultimate goal of reducing the drug development time and improving the success rate of clinical trials. These miniature devices are cost-effective as they enable high throughput drug screening and drug response to be tested with low reagent consumption [1]. Moreover, organ-on-chips can facilitate the screening of biological and chemical parameters in the cellular microenvironment by incorporating sensing technologies [2]. This can offer in situ monitoring alternatives to conventional assays and simplified assays without the need for sample collection and preparation and by using significantly less reagents. Electrochemical analytical methods are potential techniques that can be incorporated into organ-on-chip devices to enable in situ analyte detection. However, the conventional techniques such as high-performance liquid chromatography (HPLC) and gas chromatography, known for highly precise and selective measurements, are time-consuming due to sample preparation/derivatization and require large volumes of organic solvents, which results in their high cost of use [3]. Despite the progress in organ-on-chips technology, there remains a scarcity of knowledge of how organ-on-chip devices can be effectively extended as in situ sensing platforms for the quantitative monitoring of pharmaceutical compounds transport across the cell layers in drug delivery assessments.