Polymer nanoparticles have received significant interest within the pharmaceutical industry; they are largely exploited for targeted drug delivery and controlled drug release. Degradation time is one of the most important properties of drug delivery vehicles, and is the discriminating factor in the selection of the specific drug delivery system. Nanoparticles can be generated from a range of polymers, ranging from block copolymers such as PLGA to phospholipids to form liposomes. These two materials are the most commonly used biodegredable materials for the delivery of both hydrophilic and hydrophobic compounds such as drugs, bioactives and genetic materials.

 

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Does size really matter?

In a single word, yes! Nanoparticle size has a direct impact on the manner in which their contents are released, which is vital in e.g. drug delivery applications. Particle size can impact the efficiency and duration of drug release, and thus the length of time needed between treatments.

 

How does microfluidic technology help?

Microfluidics provides a tool to manipulate liquids, gases, droplets, cell and particles within micro-channel geometries. The generation of nanoparticles involves controlling the precipitation of a material during the combination of two miscible fluids, which are brought together via a specific chip geometry. The particles can be stabilized using surfactants to avoid coagulation and separation.

Among its various advantages, microfluidic technology has the ability to create three-dimensional flow patterns that achieve precise control over immiscible and miscible fluid mixing. 

Microfluidic synthesis

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. Another 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.

Microfluidic Nanoparticle Synthesis

Hydrodynamic flow focusing

The nanoparticle formation process can be carried out in a microfluidic device using the hydrodynamic flow focusing method. The flow of the polymer-containing stream is focused into a thin jet between two converging water streams with higher flow rates. As this focused stream containing dissolved polymer is established, the diffusion of the solvent out of the focused stream and the diffusion of water into the focused stream occurs, destabilising the polymer solution. This leads to nanoprecipitation of particles at the interface between these two fluids in the microfluidic channel. The particle size can be controlled by the presence of a surfactant in the aqueous phase, which inhibits further particle growth.

PLGA nanoparticles are generated by a flow of the dissolved PLGA polymer in acetone, which is surrounded by an antisolvent phase of water containing a surfactant. This process is used to enhance precipitation the and give a well-controlled particle size distribution.

Microfluidic Nanoparticle Synthesis Systems

System solutions

Dolomite’s Nanoparticle Generation Systems are a specialised solution for this application, they adapt varied microfluidic methods to generate monodisperse particles or emulsions, providing precise product characteristics, reproducibility and effortless scale-up.

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Further reading

Methods of diverse API encapsulation in polymer beads
Microfluidics Blog

Methods of diverse API encapsulation in polymer beads

Read about microfluidic methods to encapsulate organic soluble and water soluble APIs in PLGA particles.

 Continuous microfluidic synthesis of PLGA nanoparticles
Application Notes

Continuous microfluidic synthesis of PLGA nanoparticles

Methodology for production of monodisperse PLGA nanoparticles in sizes ranging from 42 nm to 95 nm using micromixing chip.

Design and self-assembly of PBLG-b-ELP hybrid diblock copolymers based on synthetic and elastin-like polypeptides
Publications

Design and self-assembly of PBLG-b-ELP hybrid diblock copolymers based on synthetic and elastin-like polypeptides

Read about how the precision synthesis and self-assembly of amphiphilic copolypeptides containing a recombinant elastin-like polypeptide (ELP) block used as a macroinitiator for the ring opening polymerization (ROP) of γ-benzyl-L-glutamate (γ-BLG NCA).

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