322e Microfluidic Assembled Lipopolyplex for Antisense Oligonucleotide Delivery

Chee Guan Koh, Department of Chemical and Biomolecular Engineering, The Ohio State University, 140 West 19th Avenue, Columbus, OH 43210, Xulang Zhang, NSF Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, 140 West 19th Avenue, Columbus, OH 43210, and L. James Lee, Chemical and Biomolecular Engineering, The Ohio State University, 125 Koffolt Labs, 140 W 19th Ave, Columbus, OH 43210.

For therapeutics applications, small and uniformly sized nanoparticles, polymer-based (polyplex) and lipid-based (lipopolyplex), are important for successful and efficient in vitro and in vivo gene/drug delivery. Nanoparticles, e.g. liposomes, have been studied extensively as nanocarriers because of their biocompatibility and ability to incorporate drug molecules. Conventional bulk mixing (BM) method of producing liposomes requires mixing of multiple reagents and postprocessing steps such as sonication or membrane extrusion to produce small and uniformly sized nanoparticles. Therefore, in this study, microfluidic devices and novel micromixers were developed for assembling lipopolyplex nanoparticles. The size, surface charge, morphology, and gene/drug encapsulation of the nanoparticles were characterized using dynamic light scattering, zeta potential measurement, atomic force microscopy, cryo-TEM, and gel electrophoresis. Nanoparticles encapsulating antisense oligonucleotides synthesized were evaluated for downregulation of Bcl-2, an antiapoptotic protein commonly overexpressed in many cancer cells.