Microfluidic assembly of cationic-β-cyclodextrin: hyaluronic acid-adamantane host:guest pDNA nanoparticles

摘要

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 microreactor 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 ξ-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 experiments. Our findings suggest that micro-fluidic reactors offer an attractive method for assembling reproducible, size-controlled complexes from multi-component transfection complex assemblies.