Hyaluronic acid-based nanoparticles for protein delivery: Systematic examination of microfluidic production conditions

Enrica Chiesa, Antonietta Greco, Federica Riva, Rossella Dorati, Bice Conti, Tiziana Modena, Ida Genta

Research output: Contribution to journalArticlepeer-review


Hyaluronic acid-based nanoparticles (HA NPs) can be used to deliver a protein cargo to cells overexpressing HA receptors such as CD44 since they combine the low toxicity of the carrier and the retention of the protein integrity with the receptor-mediated internalization. HA properties play a crucial but sometimes unclear role in managing the formation and stability of the meshwork, cell interactions, and ultimately the protein entrapment efficacy. Nowadays, microfluidic is an innovative technology that allows to overcome limits linked to the NPs production, guaranteeing reproducibility and control of individual batches. Taking advantage of this technique, in this research work, the role of HA weight average molecular weight (Mw) in NPs formation inside a microfluidic device has been specifically faced. Based on the relationship between polymer Mw and solution viscosity, a methodological approach has been proposed to ensure critical quality attributes (size of 200 nm, PDI ≤ 0.3) to NPs made by HA with different Mw (280, 540, 710 and 820 kDa). The feasibility of the protein encapsulation was demonstrated by using Myoglobin, as a model neutral protein, with an encapsulation efficiency always higher than 50%. Lastly, all NPs samples were successfully internalized by CD44-expressing cells.

Original languageEnglish
Article number1565
Issue number10
Publication statusPublished - Oct 2021


  • CD44 targeting
  • Hyaluronic acid
  • Hyaluronic acid-based nanocarriers
  • Microfluidics
  • Protein delivery
  • Protein encapsulation efficiency

ASJC Scopus subject areas

  • Pharmaceutical Science


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