Microfluidic devices as tools for mimicking the in vivo environment

Ziółkowska, Karina; Kwapiszewski, Radosław; Brzózka, Zbigniew

doi:10.1039/c0nj00709a

Cited by 106 publications

(73 citation statements)

References 165 publications

(248 reference statements)

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“…One promising approach for the realization of such predictive in vitro experiments is microfluidics [18,19]. There are already a broad range of experimental settings in which such an approach is used, e.g.…”

Section: Introductionmentioning

confidence: 99%

A microfluidics approach to study the accumulation of molecules at basal lamina interfaces

et al. 2015

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For an efficient distribution of drugs and drug carriers through biological barriers such as the vascular system, the size and surface properties of nanoparticles and molecules play a key role. To screen for important parameters which determine the ability of drugs or drug carriers to translocate through complex biological barriers, an in vitro assay which correctly predicts the behavior of those objects in vivo would be highly desirable. Here, we present a microfluidic setup to probe the diffusive spreading of molecules with different net charges and molecular weights through a basal lamina interface - a biopolymer system which contributes to the barrier function of the vascular system and the skin. From our data, we find a charge dependent accumulation of molecules at the gel interface which is consistent with transient binding of those molecules to the gel constituents. We also observe a similar charge-dependent accumulation of molecules in living mice where the test molecules colocalize with collagen IV, a key component of the basal lamina. Our assay may serve as a platform to perform penetration experiments with even more complex interfaces combining cellular barriers with biopolymer coatings.

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Section: Introductionmentioning

confidence: 99%

A microfluidics approach to study the accumulation of molecules at basal lamina interfaces

et al. 2015

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“…13,14 Some devices were recently used for drug testing on carcinoma spheroids. [15][16][17] Coculture spheroids for investigating cell-cell interactions in a 3D environment have also been implemented. 18,19 Delicately designed microfluidic devices can provide continuous medium perfusion and better oxygen exchange for spheroid culture.…”

Section: Introductionmentioning

confidence: 99%

Migration and vascular lumen formation of endothelial cells in cancer cell spheroids of various sizes

Patra

Peng²,

Peng

et al. 2014

Biomicrofluidics

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We developed a microfluidic device to culture cellular spheroids of controlled sizes and suitable for live cell imaging by selective plane illumination microscopy (SPIM). We cocultured human umbilical vein endothelial cells (HUVECs) within the spheroids formed by hepatocellular carcinoma cells, and studied the distributions of the HUVECs over time. We observed that the migration of HUVECs depended on the size of spheroids. In the spheroids of $200 lm diameters, HUVECs migrated outwards to the edges within 48 h; while in the spheroids of $250 lm diameters, there was no outward migration of the HUVECs up to 72 h. In addition, we studied the effects of pro-angiogenic factors, namely, vascular endothelial growth factor (VEGF) and fibroblast growth factor (b-FGF), on the migration of HUVECs in the carcinoma cell spheroid. The outward migration of HUVECs in 200 lm spheroids was hindered by the treatment with VEGF and b-FGF. Moreover, some of the HUVECs formed hollow lumen within 72 h under VEGF and b-FGF treatment. The combination of SPIM and microfluidic devices gives high resolution in both spatial and temporal domains. The observation of HUVECs in spheroids provides us insight on tumor vascularization, an ideal disease model for drug screening and fundamental studies.

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“…Confocal laser microscopy and flow cytometry data indicated that TK-FITC could specifically recognize Caco-2 cells and has a high affinity for Caco-2 cells (Figure 3). However, in vivo and in vitro environments are significantly different (Ziolkowska et al, 2011); thus, it is difficult to extrapolate data from in vitro experiments to possible effects in vivo (Yamada & Cukierman, 2007). Consequently, a mimicking in vivo circumstance technique is necessary to investigate the targeting of this ligand.…”

Section: Discussionmentioning

confidence: 99%

A new peptide ligand for colon cancer targeted delivery of micelles

Ren

Song

et al. 2015

Drug Delivery

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Ligands are an imperative part of targeted drug delivery systems, and choosing a ligand with high affinity is a subject of considerable interest. In this study, we first synthesized a 12-residue peptide (TK) that interacts with integrin a 6 b 1 overexpressed on colonic cancer cells. The molecular binding affinity assay indicated that TK had a high binding affinity for integrin a 6 b 1 . The results of cellular and tumor spheroid uptake suggested that TK peptide not only increases Caco-2 cells uptake, but also effectively increases penetration of the tumor spheroids. TK-conjugated PEG-PLA was synthesized to prepare a novel PEG-PLA micelles loading DOX or coumarin-6 (TK-MS/DOX or TK-MS/C6). The obtained TK-MS/DOX exhibited uniform, spherical shape with a size of 23.80 ± 0.32 nm and zeta potential of 12.21 ± 0.31 mV. The release behavior of DOX from micelles were observed no significant changes after TK modification, however, the release profile exhibited pH-sensitive properties. Compared with MS/DOX, TK-MS/DOX exhibited significantly stronger cytotoxicity for Caco-2. Confocal laser microscopy and flow cytometry data further indicated that the targeting micelles not only had higher uptake by Caco-2 cells, but also more effectively penetrated the tumor spheroids. Therefore, TK peptide appears to be suitable as a targeting ligand with potential applications in colonic targeted therapy. KeywordsColonic drug delivery, DOX, integrin a 6 b 1 receptor, micelles, peptide ligand History

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Microfluidic devices as tools for mimicking the in vivo environment

Cited by 106 publications

References 165 publications

A microfluidics approach to study the accumulation of molecules at basal lamina interfaces

A microfluidics approach to study the accumulation of molecules at basal lamina interfaces

Migration and vascular lumen formation of endothelial cells in cancer cell spheroids of various sizes

A new peptide ligand for colon cancer targeted delivery of micelles

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