Microfluidic Abstract
- 1. Microfluidic Assembly of Lipid-Based Nanoparticles for Improved Anticancer Drug Delivery The expression of the oligodeoxyribonucleotide (ODN) molecule g3139 has been shown to downregulate the expression of the bcl-2 antiapoptotic protein, allowing for cells to undergo the process of cellular apoptosis, or programmed cell death. The underexpression of apoptotic proteins in cells can lead to the uncontrolled growth of cells into cancerous tumors. The ability to successfully deliver the g3139 molecule to targeted regions of the body could dampen the expression of the bcl-2 protein, therefore enabling cells to undergo apoptosis and prohibit further uncontrolled growth. Lipid- based nanoparticles (LNPs) are recognized as a potential targeted delivery method. Particle size is an important factor in determining cellular uptake and in vivo biodistribution of LNPs. In this research project, we adapted a new microfluidic technology to create LNPs ranging from 90 nm to over 400 nm. A range of LNPs encapsulating fluorescently labeled siRNA were synthesized and used in in vivo and in vitro studies to determine which particle sizes were most effective for delivery to targeted tumor cells. Gene silencing activity of siRNA by various sized LNPs was determined using RT-PCR. The IVIS imaging system was used to determine the biodistribution of a range of fluorescently labeled LNPs. Extensive testing determined that, on average, slower flow rates resulted in larger nanoparticles, regardless of the siRNA and lipid formulations used, and nanoparticle size did not affect the gene silencing ability of siRNA loaded in LNPs in vitro. It was also found that larger LNPs delivered via passive targeting were most effective in reaching a targeted tumor, but also impacted the liver. The results collected demonstrate that drug delivery via LNPs is a promising technique to improve the effectiveness of anticancer treatments.