. 2019 Aug 1;9(3):360–373. doi: 10.15171/apb.2019.043

Table 3. Organ-on-a-chip and 2D microfluidic models for drug delivery .

Cells	Culture	Nanoparticle	System	Brief summary of the study	Ref.
A549	2D dish culture	Cerium oxide NPs	-	Oxidative stress and cytotoxicity effects of CeO2 NPs on A549 cells	¹⁶⁶
Human bronchoalveolar carcinoma	2D dish culture	Silica NPs	-	The effect of Silica NPs size on toxicity in bronchoalveolar carcinoma	¹⁶⁷
LCC6/Her2	Droplet based microfluidics	DOX loaded CaCO3-NPs	In this system, the alginate beads were trapped in micro-sieve structures for cell culture in a continuous perfusion system. The environment permitted cell proliferation and the formation of multicellular spheroids.	Dose dependent cytotoxic effects of DOX loaded CaCO2-NPs	¹⁶⁸
Human endothelial cell	2D microfluidic channel	MSN	A simple microfluidic platform with precisely controlled shear stress conditions	Shear stress and endothelial cytotoxicity	¹⁶⁹
MDA-MB-435	Organ-on-a-chip (spheroid formation)	Gold NPs	A tumor-on-a-chip system where incorporation of tumor-like spheroids into a microfluidic channel permits real-time analysis of NP accumulation at physiological flow conditions.	Developing a tumor-on-a-chip system to study the transport of gold NPs through a 3D tissue environment and characterizing NPs within a tumor tissue.	¹⁷⁰
Hy926 and human platelet	2D microfluidic channel	FMS-NPs	The impact of sub-50 nm diameter mesoporous silica nanoparticles on platelet function is investigated using a microfluidic platform to model blood vessel characteristics	The effect of FMS-NPs on platelet aggregation	¹⁷¹
HUVEC	2D microfluidic channel	Lipid-polymer NPs	Endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer.	Microfluidic model of atherosclerosis to assessment of NPs endothelial translocation	¹⁷²
MCF-7 and MVECs	Organ-on-a-chip (Pseudo 3D)	Fluorescent NPs	This model, consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid	Transport of NPs within the tumor	¹⁷³
Caco-2, TH29-MTX and HepG2/C3A	2D microfluidic channel	carboxylated polystyrene NPs	To construct this system, we combined in vitro models of the human intestinal epithelium, represented by a co-culture of Caco-2, TH29-MTX, and HepG2/C3A cells, within one microfluidic device.	Detection of liver injury using GI tract-liver-other tissue system	¹⁷⁴
HUVEC	2D microfluidic channel	Gold NPs	The tests performed in the microfluidic device were also run in multiwells, where no flow is present	Flow dependent cytotoxicity effects of gold NPs on endothelial	¹⁷⁵
MCF-7, MDA-MB-231, and SUM-159PT	Organ-on-a-chip (3D gel pattering)	Dox-HANP	Three types of human breast cancer cell lines including MCF-7, MDA-MB-231, and SUM-159PT were cultured on a 3D platform, and their drug response and resistance to doxorubicin were characterized	The effects of NPs mediated drug delivery	¹⁷⁶
HUVEC	2D microfluidic channel	Gold NPs	A microfluidic device to observe how HUVEC viability changes when subject to a continuous flow of culture medium.	The effect of shear stress and gold NPs size on endothelial cytotoxicity	¹⁷⁷
HUVEC	Organ-on-a-chip	HDL mimetic NPs	A micro-engineered three-dimensional vascular system	The effect of HDL mimetic NPs on endothelial cells	¹⁷⁸

CaCO3: calcium carbonate; CeO2: cerium oxide; DOX: doxorubicin; FMS: fluorescent mesoporous silica; MSN: mesoporous silica nanoparticle; HDL: high density lipoprotein; HANP: hyaluronic acid nanoparticle; gH625: membranotropic peptide; NPs: nanoparticles.