4.6 Article

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

Journal

Publisher

ELSEVIER
DOI: 10.1016/j.nano.2022.102560

Keywords

Microfluidics; Nanoparticle size; Chitosan; Hyaluronic acid; Inflammation

Funding

  1. Fundacao para a Ciencia e a Tecnologia (FCT) [NORTE-01-0145-FEDER-000021]
  2. PATH program [PD/BD/143140/2019]
  3. Cells4_IDs [PD/00169/2013]
  4. Norte2020 [PTDC/BTM-SAL/28882/2017]

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In this study, a microfluidic method was proposed to synthesize chitosan-hyaluronic acid nanoparticles (NPs), which showed smaller and more uniform size compared to the traditional dropwise method. The obtained NPs demonstrated potential in reducing inflammatory molecules in macrophages and fibroblasts. This study provides a new approach for the synthesis of nanocarriers based on bioactive macromolecules.
Chitosan (CHIT) and hyaluronic acid (HA) are two polysaccharides (PSs) with high value in several biomedical applications. In this study, we present a microfluidic method to synthetize CHIT-HA NPs to overcome the disadvantages of the dropwise approach generally used for nanoprecipitation of polyelectrolyte complexes. The proposed microfluidic approach enables to generate monodisperse suspensions of NPs with asymptotic to 100 nm of size compared to the dropwise method that generated asymptotic to 2 times bigger NPs. Finally, we evaluated the potential of obtained NPs in an inflammatory scenario. The treatment with NPs led to the reduction of the main inflammatory molecules produced by macrophages (PGE2, IL-6, IL-8, MCAF and TNF-alpha) and fibroblasts (IL-1 alpha, PGE2, TNF-alpha) stimulated with lipopolysaccharide or conditioned medium, respectively. This study demonstrates that our approach can be used to enhance the synthesis of nanocarriers based on bioactive macromolecules. (C) 2022 Elsevier Inc. All rights reserved.

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