Controllable Microfluidic Production of Drug-Loaded PLGA Nanoparticles Using Partially Water-Miscible Mixed Solvent Microdroplets as a Precursor

We present a versatile continuous microfluidic flow-focusing method for the production of Doxorubicin (DOX) or Tamoxifen (TAM)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). We use a partially water-miscible solvent mixture (dimethyl sulfoxide DMSO+ dichloromethane DCM) as precursor drug/polymer solution for NPs nucleation. We extrude this partially water-miscible solution into an aqueous medium and synthesized uniform PLGA NPs with higher drug loading ability and longer sustained-release ability than conventional microfluidic or batch preparation methods. The size of NPs could be precisely tuned by changing the flow rate ratios, polymer concentration, and volume ratio of DCM to DMSO (VDCM/VDMSO) in the precursor emulsion. We investigated the mechanism of the formation of NPs and the effect of VDCM/VDMSO on drug release kinetics. Our work suggests that this original, rapid, facile, efficient and low-cost method is a promising technology for high throughput NP fabrication. For the two tested drugs, one hydrophilic (Doxorubicin) the other one hydrophobic (Tamoxifen), encapsulation efficiency (EE) as high as 88% and mass loading content (LC) higher than 25% were achieved. This new process could be extended as an efficient and large scale NP production method to benefit to fields like controlled drug release and nanomedicine.

• Publication year

  2017

• Venue

  Scientific Reports

• Publication date

  2017-07-06

• Fields of study

  Medicine, Materials Science, Chemistry, Engineering

• Identifiers
  DOI 10.1038/s41598-017-05184-5PMID 28684775PMCID 5500499
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Inhibition of the cancer-associated TASK 3 channels by magnetically induced thermal release of Tetrandrine from a polymeric drug carrier.

  2016cited by this paper
• Methods for production of uniform small-sized polymersome with rigid membrane

  2016cited by this paper
• The Past and the Future.

  2016influential reference
• Modeling size controlled nanoparticle precipitation with the co-solvency method by spinodal decomposition.

  2016cited by this paper
• Evaporation of pinned droplets containing polymer – an examination of the important groups controlling final shape

  2015cited by this paper
• Microfluidic assembly of monodisperse multistage pH-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery.

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• Microfluidic conceived drug loaded Janus particles in side-by-side capillaries device.

  2014cited by this paper
• Size controlling of monodisperse carboxymethyl cellulose microparticles via a microfluidic process

  2014cited by this paper
• Controlled emulsion droplet solvent evaporation for particle production

  2013cited by this paper
• Vesicular self-assembly of colloidal amphiphiles in microfluidics.

  2013cited by this paper
• One-step fabrication of core-shell structured alginate-PLGA/PLLA microparticles as a novel drug delivery system for water soluble drugs.

  2013cited by this paper
• Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study.

  2013cited by this paper
• Particle formation in the emulsion-solvent evaporation process.

  2013cited by this paper
• Advanced materials and processing for drug delivery: the past and the future.

  2013cited by this paper
• Microfluidic synthesis of advanced microparticles for encapsulation and controlled release.

  2012cited by this paper
• Size-tunable nanoparticles composed of dextran-b-poly(D,L-lactide) for drug delivery applications

  2011cited by this paper
• Nanoprecipitation and nanoformulation of polymers: from history to powerful possibilities beyond poly(lactic acid)

  2011cited by this paper
• PLGA micro/nanosphere synthesis by droplet microfluidic solvent evaporation and extraction approaches.

  2010cited by this paper
• Doxorubicin as a molecular nanotheranostic agent: effect of doxorubicin encapsulation in micelles or nanoemulsions on the ultrasound-mediated intracellular delivery and nuclear trafficking.

  2010cited by this paper
• Transient surface tension in miscible liquids.

  2010cited by this paper
• A simple method to achieve high doxorubicin loading in biodegradable polymersomes.

  2010cited by this paper
• Microfluidics in inorganic chemistry.

  2010cited by this paper
• Generation of monodisperse silk microspheres prepared with microfluidics.

  2010cited by this paper
• Synthesis of micro and nanostructures in microfluidic systems.

  2010cited by this paper
• Single-step assembly of homogenous lipid-polymeric and lipid-quantum dot nanoparticles enabled by microfluidic rapid mixing.

  2010cited by this paper
• Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications.

  2010cited by this paper
• Synthesis of goethite by separation of the nucleation and growth processes of ferrihydrite nanoparticles using microfluidics.

  2009cited by this paper
• Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery.

  2009cited by this paper
• Tortuosity of unsaturated porous fractal materials.

  2008cited by this paper
• Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles.

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• Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods.

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• The origins and the future of microfluidics

  2006cited by this paper
• Synthesis and characterization of PLGA nanoparticles

  2006cited by this paper
• Synthesis of monodisperse biodegradable microgels in microfluidic devices.

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• Perfectly monodisperse microbubbling by capillary flow focusing.

  2001cited by this paper
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  2001cited by this paper
• Doxorubicin-loaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance.

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• Temperature-dependent self-diffusion coefficients of water and six selected molecular liquids for calibration in accurate 1H NMR PFG measurements

  2000cited by this paper
• Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method.

  1999cited by this paper
• Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D, L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior.

  1993cited by this paper
• Biological applications of scanning tunnelling microscopy

  1993cited by this paper
• Nanocapsule formation by interfacial polymer deposition following solvent displacement

  1989cited by this paper
• Polymer Handbook

  1972cited by this paper
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  1950cited by this paper
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