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      Studies of nanoparticle delivery with in vitro bio-engineered microtissues

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          Abstract

          A variety of engineered nanoparticles, including lipid nanoparticles, polymer nanoparticles, gold nanoparticles, and biomimetic nanoparticles, have been studied as delivery vehicles for biomedical applications. When assessing the efficacy of a nanoparticle-based delivery system, in vitro testing with a model delivery system is crucial because it allows for real-time, in situ quantitative transport analysis, which is often difficult with in vivo animal models. The advent of tissue engineering has offered methods to create experimental models that can closely mimic the 3D microenvironment in the human body.

          This review paper overviews the types of nanoparticle vehicles, their application areas, and the design strategies to improve delivery efficiency, followed by the uses of engineered microtissues and methods of analysis. In particular, this review highlights studies on multicellular spheroids and other 3D tissue engineering approaches for cancer drug development. The use of bio-engineered tissues can potentially provide low-cost, high-throughput, and quantitative experimental platforms for the development of nanoparticle-based delivery systems.

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          Highlights

          • This paper overviews the designs, analyses, and applications of various nanoparticles studied for drug delivery.

          • The emphasis is on in vitro engineered tissue models used for the evaluation of nanoparticle transport.

          • The in vitro models allow for in situ quantitative transport analysis, which is often difficult with in vivo models.

          • Tissue mechanical characteristics and structural heterogeneity are emerging topics for the study of nanoparticle delivery.

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          Most cited references157

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          Drug resistance and the solid tumor microenvironment.

          Resistance of human tumors to anticancer drugs is most often ascribed to gene mutations, gene amplification, or epigenetic changes that influence the uptake, metabolism, or export of drugs from single cells. Another important yet little-appreciated cause of anticancer drug resistance is the limited ability of drugs to penetrate tumor tissue and to reach all of the tumor cells in a potentially lethal concentration. To reach all viable cells in the tumor, anticancer drugs must be delivered efficiently through the tumor vasculature, cross the vessel wall, and traverse the tumor tissue. In addition, heterogeneity within the tumor microenvironment leads to marked gradients in the rate of cell proliferation and to regions of hypoxia and acidity, all of which can influence the sensitivity of the tumor cells to drug treatment. In this review, we describe how the tumor microenvironment may be involved in the resistance of solid tumors to chemotherapy and discuss potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumor microenvironment.
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            Droplet microfluidics.

            Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                30 June 2020
                December 2020
                30 June 2020
                : 5
                : 4
                : 924-937
                Affiliations
                [1]Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Rd, Storrs, CT, 06269, USA
                Author notes
                []Corresponding author. Biomedical Engineering University of Connecticut, 260 Glenbrook Rd, Unit 3247, Storrs, CT, 06269-3247, USA. hoshino@ 123456engr.uconn.edu
                Article
                S2452-199X(20)30119-5
                10.1016/j.bioactmat.2020.06.016
                7330434
                32637755
                b91bfa1f-9fea-4a3a-8f9a-3343ecec620c
                © 2020 [The Author/The Authors]

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 February 2020
                : 12 June 2020
                : 22 June 2020
                Categories
                Article

                nanoparticles,drug delivery,in vitro tissue model,multicellular spheroid

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