Vessel-on-a-Chip Development to Understand Systemically Administered NanoparticlesVessel-on-a-Chip Development to Understand Systemically Administered Nanoparticles

Abstract

Nanomedicine holds great promise for treating complex diseases, particularly due to its unique ability to sustain and target drug delivery. However, the validation method has been a great challenge to the development of nano-based therapeutics. The main reason is the unpredictable delivery dosage and lack of adequate preclinical trial methods that replicate the human biological environment for testing nanomedicine. This project introduced organ-on-a-chip (OOC) method to mimic the human vascular environment in vitro for studying the transportation of nanoparticles in human vessels. The goal was to use commercially available resources to increase the generalization and ease of adaptability for other labs working within the field of nanomedicine. The build-up of this vessel-on-a-chip (VoC) was successfully achieved using a microfluidic chip from Ibidi along with a microfluidic set-up to stimulate the human umbilical vein endothelial cells (HUVEC) seeded in the chip. The cells formed an oriented endothelial cell (EC) monolayer mimicking the endothelium of a capillary under a 24-hour flow of 10dyn/cm2. This monolayer acted as a barrier preventing NPs from extravasating into the tissue, which is an important aspect of nanoparticle delivery. In addition, a computational fluidic dynamic (CFD) simulation approach was conducted to further enhance the predictability of NP transportation. The microfluidic simulation helped to explain unexpected phenomena during the flow experiment.Although the blood flow simulation had some limitations, it could provide useful insights when evaluating a potential uptake amount of NPs when administered systemically. This integrated study of combining VOC with CFD simulation enhances our understanding of NP behavior in human vessels but requires further optimization to be fully operational.