Microfluidics application note
Preparation of PLGA nanoparticles by hydrodynamic flow focusing
PLGA nanoparticles
PLGA nanoparticles generation (Poly(lactic-co-glycolic acid)) is of great interest for biomedical applications and especially for drug delivery. These polymeric nanoparticles (NPs) are valued for their biocompatibility and biodegradability. For most biomedical applications implying the use of PLGA nanoparticles synthesis, it is important to have a monodisperse solution of NPs, i.e., a narrow size distribution. Hence, the preparation of PLGA nanoparticles in microfluidics is more suitable for that particular purpose than common batch methods. For more complete information, the reader is advised to have a look at the review here. Other nanoparticles, like lipid nanoparticles, can also be synthesized with the same instruments and minor modifications to this protocole, contact our experts for more information.
Watch the webinar by our researcher Audrey Nsamela about nanoparticle fabrication!
Advantages of this setup for PLGA nanoparticle preparation
This application note describes how to fabricate PLGA nanoparticles with an hydrodynamic flow focusing microfluidic chip, use the OB1 flow controller and digital flow sensors to maintain a precise flow rate ratio and produce highly monodisperse nanoparticles.
In this setup, the nanoparticles are produced by a process called nanoprecipitation. For more general information, read also our review on microfluidic nanoparticle synthesis. Using this microfluidic setup to manufacture PLGA NPs allows you to easily tune their sizes and concentration by varying the flow rates of the respective reagents (aqueous and polymeric). The NPs produced have less batch-to-batch variability and a narrow size distribution with a polydispersity index (PDI) typically below 0.2.
Some of the main applications of PLGA NPs include (Danhier et al., 2012):
- Drug delivery
- Cancer treatment
- Inflammatory diseases targeting
- Cardiovascular diseases
- Neurological diseases
- Regenerative medicine
- Vaccines
List of components for a microfluidic PLGA nanoparticle synthesis setup
Flow sensor (MFS3 and MFS4)
Fluidic 386 chip from Microfluidic ChipShop Gmbh
Setup diagram for PLGA nanoparticles preparation
HARDWARE:
- Pressure & flow controller: Impose a given pressure in order to create a stable and pulseless flow.
- Reservoirs: Contains your aqueous and polymeric solutions. Various cap sizes are available, from Eppendorfs to bottles.
- Flow sensors: Monitor and control the flow rate in real time.
- Microfluidic chip: Purchased from Microfluidic ChipShop and made in a solvent compatible material.
- Computer with ESI software: Control all the parameters with our software and automate your experiment by creating sequences.
REAGENTS:
- PLGA solution (Resomer 503 H at 50 mg/mL) in solvent
- Solvent (acetonitrile)
- Surfactant solution (PVA 1%)
Learn how to set up PLGA Nanoparticle generation in your lab:
PLGA nanoparticle preparation protocol
- Fill your entire system with acetonitrile and water to optimize the resistance of your setup and check for leaks.
- Stop the pressure and exchange the reservoirs to connect your PLGA in acetonitrile and surfactant in water solutions to your setup.
- Set the flow rates of both solutions to have the desired flow rate ratio. A MFS4 flow sensor can be used for the water solution and a MFS3 flow sensor can be used for the PLGA solution.
- Collect the PLGA nanoparticles in a collection tube.
- Centrifugate the PLGA nanoparticles to remove excess surfactant.
Results
The selected design of the microfluidic chip (Fluidic 386) is suitable to produce highly monodisperse PLGA nanoparticles ranging from 160 to 230 nm.
Hints & tips
Our team of experts can help you perform your experiment, improve the configuration of the setup for your specific application and tackle any issues you could face.
We can help you:
- Perform a proper calibration of your flow sensors
- Avoid clogging which is detrimental to obtain a good flow control
- Easily purge air and the remaining nanoparticles from your system
- Control the flow focusing by pressure or by flow rate
- Using resistance tubing
- Perfectly and quickly stop the flow
- And a lot more!
Application note written by Audrey NSAMELA – Acknowledgement: This work was done thanks to the funding of European Union’s Horizon 2020 research and innovation programme (ActiveMatter H2020-MSCA-ITN-2018-Action “Innovative Training Networks”, Grant agreement number: 812780).
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