Applications

Polymer Nanoparticle Synthesis

What is a polymer?

A polymer is a macromolecule composed by many repeated units (or monomers) which is characterised by a wide range of mechanical and chemical properties. Polymers are largely employed in our everyday lives in many different applications.

Recently polymer nanoparticles have received a significant interest within pharmaceutical industry. Polymer particle systems have been largely exploited in the fields of targeted drug delivery and controlled drug release. Degradation time is one of the most important property of the polymer and is the discriminating factor in the selection of the specific drug delivery system. Natural based polymers, such as agarose and alginate, or synthetic biodegradable polymer, such as polyesters and polyamides, can be used for targeted drug delivery. Among them, PLGA is the most common biodegradable used to deliver both hydrophilic and hydrophobic drugs. Our application note ‘Continuous Microfluidic Synthesis of PLGA Nanoparticles by Micromixing’ specifically focuses on PLGA nanoparticles production.

Highlights of microfluidic technology

Unlike conventional methods such as homogenization, microfluidic technologies enable production of hundreds to thousands of polymer nanoparticles per second with a very narrow size distribution. Moreover, the use of continuous flow techniques provide simple methodology for high yield and high quality fabrication of polymer nanoparticles for various applications.

Synthetic and natural polymer particles represent a mobile substrate that can be biochemically tailored – this is known as surface functionalization. The process involves covalent immobilization of proteins, peptides, and nucleic acids to chemical end groups exposed on the surface of the solid particles. For example, polystyrene microspheres are ideal for protein adsorption. The most common surface treatment in drug delivery is the PEG-ylation of PLGA particles. This provides a functional site for surface conjugation of targeting agents and improves surface properties.

Micromixing method using the Dolomite Micromixer Chip. In this approach, PLGA nanoparticles are generated by solvent displacement method (1) or by rapid mixing which causes emulsion breakup to small scale (2):

       1)   Micromixing – Solvent displacement method

PLGA nanoparticles are generated by a flow of the dissolved PLGA polymer in solvent (acetone), which is surrounded by an antisolvent phase (water + surfactant), leading to nanoprecipitation of particles at the interface. Mixing is used to enhance precipitation the and give a well-controlled particle size distribution.

Micromixing-method-500x297

Schematic showing a micromixing mediated nanoparticle production strategy.

yellow-vial-25x8 -Polymer dissolved in organic solvent with high aqueous miscibility; blue-vial-25x7 – Water (surfactant); red-vial-25x8 – Polymer nanoparticles as solid content dispersed in water with residual solvent.

Colours and sizes are illustrative only and not to scale.

       2)   Micromixing – Emulsification method

The process starts with a mixture formation of synthetic polymer in DCM and water immiscible solvent. Emulsification is promoted by the particular herringbone mixing structure of the microfluidic micromixer chip. The agitation of these mixtures results in the formation of micro-emulsion which is collected in a vial or on the glass slide. This is then followed by the evaporation stage where the water-immiscible solvent (DCM) leave the mixture resulting in further polymer particle hardening and reduction in diameter to nanozise.

emulsification-method-500x228

Schematic showing an emulsification mediated nanoparticle production strategy.

yellow-vial-25x8 – Polymer dissolved in organic solvent with very low aqueous miscibility; blue-vial-25x7 – Water; red-vial-25x8 – Polymer nanoparticles as solid content dispersed in water with residual solvent.

Colours and sizes are illustrative only and not to scale.

Effective Micromixing and Emulsification ensures that the polymer is evenly distributed throughout the solution and that the particle production histories are close to identical. This results in the formation of highly monodisperse particles.

Benefits of microfluidic liposome synthesis

          High Monodispersity

  • Microfluidic techniques offer extremely consistent size of polymer particles.

          Precisely tuned particles

  • Control of the polymer particle size, shape and morphology enable users to easily reproduction of distinctive characteristics.

          Reduced reagent consumption

  • Microfluidic technology ensures almost 100% reagent consumption, reducing wastage and making synthetic polymer synthesis a cost-effective option.

          Production Prospects

  • Microfluidics is very adaptable to gain quick research results which can be easily applied for production scale up.

          Wide application fields

  • Microfluidics have a wide range of applications. From diagnostic tests and controlled drug delivery to binders for paints and varnishes.

 

Associated products

  • + Nanoparticle Generation System

    Nanoparticle Generation System

    Produce highly monodispersed polymer particles

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    Nanoparticle Generation System

    The Polymer Nanoparticle Generation System provides a solution for production of monodisperse polymer nanoparticles such as PLGA, PEG, PVC.

    Dolomite’s modular nanoparticle synthesis systems apply high shear micromixing and hydrodynamic focusing microfluidic methods for polymer particle production ranging in sizes from 50nm to 500nm. Continuous and controllable laminar flow allows the production of high-yield and high-quality polymer nanoparticles. The system provides substantial improvements in nanoparticle size distribution when compared to conventional batch methods. Additional benefits include:

    • Wide range of particle sizes ranging from 50 nm to 500 nm
    • Highly monodisperse particles with CV values between 20% and 30%
    • Precise control of size, shape and morphology of particles
    • Production rate up to few grams per day (Telos Large Scale Micro Droplet System)
    • Batch to batch reproducibility with reduced reagent consumption
    • Modular systems
    • Easy scale-up for various applications

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