Microfluidic 3D intestine tumor spheroid model for efficient in vitro investigation of nanoparticular formulations

For the treatment of intestinal tumors by oral administration of drugs, the mucus layer of the intestine represents a barrier, but also a target possibility for drug. The use of nanoparticular drug delivery systems is an important tool to improve the transport and accumulation of the drug on the target side. Therefore, specific in vitro test systems to simulate the conditions of an intestine tumor are necessary for the screening and efficiency testing of potential new nanoparticular drug delivery systems. Here, we introduce a microfluidic 3D intestine tumor spheroid model, which allows to test functionalized nanoparticles and their ability to adsorb onto and permeate over a mucus layer under dynamic conditions. More specifically, the model consists of a 3D tumor spheroid with a mucus layer and microvilli on the surface, which is placed into a microfluidic chip system. The system incorporates a fluid flow, which is an important factor in nanoparticle residence time and uptake. To test the microfluidic 3D intestine tumor spheroid model, two different nanoparticle systems surfaces-coated with Carbopol® or Pluronic® F127 were produced to test the adsorption and permeation over the mucus layer. The data showed obvious adsorptive and permeable properties of uncoated and surface-coated nanoparticles in the static and dynamic system. The 3D intestine tumor spheroid model has the potential to significantly advance the preclinical development of new drugs like nanoparticles. [Display omitted]