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Microfluidic Buffer Exchange for Interference-free Micro/Nanoparticle Cell Engineering

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Microfluidic-driven mixing of high molecular weight polymeric complexes for precise nanoparticle downsizing.

Sara Gimondi¹, Rui L Reis¹, Helena Ferreira¹

¹3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, Guimarães, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.

Nanomedicine : Nanotechnology, Biology, and Medicine

|April 13, 2022

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This study introduces a microfluidic method for synthesizing chitosan-hyaluronic acid nanoparticles, creating smaller, uniform nanocarriers. These nanoparticles effectively reduce key inflammatory molecules in both macrophages and fibroblasts.

Area of Science:

Biomaterials Science
Nanotechnology
Drug Delivery

Background:

Chitosan (CHIT) and hyaluronic acid (HA) are valuable polysaccharides for biomedical applications.
Traditional dropwise nanoprecipitation methods for polyelectrolyte complexes have limitations, often resulting in larger, less uniform nanoparticles.
There is a need for improved methods to synthesize well-defined nanocarriers for enhanced therapeutic efficacy.

Purpose of the Study:

To develop and present a microfluidic method for synthesizing chitosan-hyaluronic acid nanoparticles (CHIT-HA NPs).
To compare the characteristics of CHIT-HA NPs synthesized via microfluidics versus the traditional dropwise method.
To evaluate the anti-inflammatory potential of the synthesized CHIT-HA NPs in relevant cellular models.

Main Methods:

Keywords:

Chitosan Hyaluronic acid Inflammation Microfluidics Nanoparticle size

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Utilized a microfluidic system for the controlled synthesis of CHIT-HA NPs.
Employed nanoprecipitation technique within the microfluidic device.
Characterized nanoparticle size and monodispersity.
Assessed the impact of CHIT-HA NPs on inflammatory marker production in stimulated macrophages and fibroblasts.

Main Results:

The microfluidic method produced monodisperse CHIT-HA NPs with an average size of approximately 100 nm.
The dropwise method resulted in significantly larger nanoparticles (approximately twice the size).
CHIT-HA NP treatment reduced the production of key inflammatory molecules, including PGE₂, IL-6, IL-8, MCAF, and TNF-α in macrophages, and IL-1α, PGE₂, and TNF-α in fibroblasts.

Conclusions:

The microfluidic approach offers a superior method for synthesizing monodisperse CHIT-HA NPs compared to the dropwise method.
The synthesized CHIT-HA NPs demonstrate significant potential as anti-inflammatory agents.
This microfluidic strategy can be broadly applied to enhance the synthesis of nanocarriers based on various bioactive macromolecules.