title: Microfluidic Assembly of Cationic-β-Cyclodextrin:Hyaluronic Acid-Adamantane Host:Guest pDNA Nanoparticles.
abstract: Traditionally, transfection complexes are typically formed by bulk mixing, producing particles with high polydispersity and limited control over vector size. Herein, we demonstrate the use of a commercial micro-reactor to assemble pDNA:cationic cyclodextrin:pendant polymer nanoparticles using a layer-by-layer approach. Our studies reveal that the particles formulated via microfluidic assembly have much smaller sizes, lower polydispersity, lower ζ-potentials, and comparable cell viability and transfection profiles in HeLa cells than bulk mixed particles. The complexes also show a flow rate-dependent stability, with particles formed at slower flow rates giving rise to more stable complexes as determined by heparin challenge. Our findings suggest that microfluidic reactors offer an attractive method for assembling reproducible, size-controlled complexes from multi-component transfection complex assemblies.
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN, USA 47907. Tel: 765-494-0386.
authors.forename: Aditya
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN, USA 47907. Tel: 765-494-0386.
authors.forename: Ross
authors.initials: R
authors.lastname: Verheul
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN, USA 47907. Tel: 765-494-0386.
authors.forename: Kyle
authors.initials: K
authors.lastname: Defrees
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN, USA 47907. Tel: 765-494-0386.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Collins
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN, USA 47907. Tel: 765-494-0386.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Schuldt
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN, USA 47907. Tel: 765-494-0386.
authors.forename: Alexander
authors.initials: A
authors.lastname: Vlahu
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN, USA 47907. Tel: 765-494-0386.
authors.forename: David H
authors.initials: DH
authors.lastname: Thompson