title: Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study.
abstract: Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and reproducibility in physicochemical properties of NPs compared to bulk synthesis methods. However, applications of microfluidic synthesis are typically limited to in vitro studies due to low production rates. Herein, we report the parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a multilayer microfluidic system to enhance the production rate without losing the advantages of reproducibility, controllability, and robustness. Using parallel 3D HFF, polymeric poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) NPs with sizes tunable in the range of 13-150 nm could be synthesized reproducibly with high production rate. As a proof of concept, we used this system to perform in vivo pharmacokinetic and biodistribution study of small (20 nm diameter) PLGA-PEG NPs that are otherwise difficult to synthesize. Microfluidic parallelization thus enables synthesis of NPs with tunable properties with production rates suitable for both in vitro and in vivo studies.
  
  
  BACKGROUND
  Applications of nanoparticle synthesis with microfluidic methods are typically limited to in vitro studies due to low production rates. The team of authors of this proof-of-principle study reports on the successful parallelization of NP synthesis by 3D hydrodynamic flow focusing using a multilayer microfluidic system to enhance production rate without losing the advantages of reproducibility, controllability, and robustness.
authors: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital - Harvard Medical School, Boston, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Jong-Min
authors: JM
authors: Lim
authors: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Nicolas
authors: N
authors: Bertrand
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Pedro M
authors: PM
authors: Valencia
authors: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital - Harvard Medical School, Boston, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Minsoung
authors: M
authors: Rhee
authors: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Robert
authors: R
authors: Langer
authors: Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
authors: Sangyong
authors: S
authors: Jon
authors: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital - Harvard Medical School, Boston, MA, USA. Electronic address: ofarokhzad@zeus.bwh.harvard.edu.
authors: Omid C
authors: OC
authors: Farokhzad
authors: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: karnik@mit.edu.
authors: Rohit
authors: R
authors: Karnik
mesh_terms: D000818:Animals; D019540:Area Under Curve; D016503:Drug Delivery Systems; D015195:Drug Design; D004867:Equipment Design; D005260:Female; D006801:Humans; D057446:Hydrodynamics; D008027:Light; D008297:Male; D051379:Mice; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics / Q000379:methods*; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012542:Scattering, Radiation; D012997:Solvents; D014018:Tissue Distribution
chemical_list: D011091:Polyesters; D011108:Polymers; D012997:Solvents; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols
keywords: 3D flow focusing; Block copolymers; Microfluidics; Nanoparticles; Nanoprecipitation
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