title: Microfluidic based high throughput synthesis of lipid-polymer hybrid nanoparticles with tunable diameters.
abstract: Core-shell hybrid nanoparticles (NPs) for drug delivery have attracted numerous attentions due to their enhanced therapeutic efficacy and good biocompatibility. In this work, we fabricate a two-stage microfluidic chip to implement a high-throughput, one-step, and size-tunable synthesis of mono-disperse lipid-poly (lactic-co-glycolic acid) NPs. The size of hybrid NPs is tunable by varying the flow rates inside the two-stage microfluidic chip. To elucidate the mechanism of size-controllable generation of hybrid NPs, we observe the flow field in the microchannel with confocal microscope and perform the simulation by a numerical model. Both the experimental and numerical results indicate an enhanced mixing effect at high flow rate, thus resulting in the assembly of small and mono-disperse hybrid NPs. In vitro experiments show that the large hybrid NPs are more likely to be aggregated in serum and exhibit a lower cellular uptake efficacy than the small ones. This microfluidic chip shows great promise as a robust platform for optimization of nano drug delivery system.
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety , National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety , National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: LNM, Institute of Mechanics , Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety , National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Xuanyu
authors.initials: X
authors.lastname: Li
authors.affiliation: LNM, Institute of Mechanics , Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hu
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety , National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Jiashu
authors.initials: J
authors.lastname: Sun
authors.affiliation: Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety , National Center for NanoScience and Technology, Beijing 100190, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Jiang